KR102529550B1 - 차세대 염기서열 분석을 이용한 대장암 관련 다빈도 유전자 변이 검출을 위한 프로브 세트 - Google Patents

차세대 염기서열 분석을 이용한 대장암 관련 다빈도 유전자 변이 검출을 위한 프로브 세트 Download PDF

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KR102529550B1
KR102529550B1 KR1020200152781A KR20200152781A KR102529550B1 KR 102529550 B1 KR102529550 B1 KR 102529550B1 KR 1020200152781 A KR1020200152781 A KR 1020200152781A KR 20200152781 A KR20200152781 A KR 20200152781A KR 102529550 B1 KR102529550 B1 KR 102529550B1
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김황필
문성태
노한성
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Abstract

대장암의 다빈도 유전자 변이 탐색을 위한 염기서열 분석 기반 프로브 서열 및 조성물에 관한 것이다. 본원에 따른 서열 및 조성물은 프로브와 유전자 간의 혼성화 방법을 이용한 NGS기반의 타겟 시퀀싱 기술로 기존의 microarray 방법이나 PCR 방법에 비해 많은 유전자의 보다 넓은 타겟 염기서열을 비교적 낮은 비용으로 정확하고 민감하며 높은 재현성으로 분석할 수 있다.

Description

차세대 염기서열 분석을 이용한 대장암 관련 다빈도 유전자 변이 검출을 위한 프로브 세트 {Probe Set for the Detection of High Frequency Gene Mutations related to Colorectal Cancer using Next-Generation Sequencing System}
염기서열 분석 기반 대장암의 다빈도 유전자 변이 탐색을 위한 프로브 서열과 관련된 것이다.
암은 인류의 건강을 위협하는 대표적인 질병으로서 산업화된 국가에서 단일 질병으로는 가장 대표적인 사망 원인이다. 암의 발생원인은 아직도 규명되지 않고 있으나 내적 요인인 유전적 요소와 외적 요인인 암 발생 유발요소로 작용되는 발암화학물질, 계속적인 염증과 손상, 암 유발 바이러스 감염의 복합적 요소가 작용하는 것으로 간주된다. 유전적 요소에 대해서는 동물실험상 많은 입증이 있으나 인간의 암에 대한 작용 여부는 망막아세포종이나 가족적 대장 이종증 등 일부를 제외하고는 확실한 증거가 없으며, 오히려 외적 요인인 환경적 요소와 구별하기 어려운 실정이다.
대장암은 현재 우리나라에서 전체 3번째의 높은 발생률을 가지고 있으며, 남자에서 2번째, 여자에서 3번째의 높은 발생률을 보여 그 발생률과 사망률이 계속 증가하고 있는 추세이다. 또한 생활양식이 점차 서구화되어 가는 것을 고려하면 대장암의 증가는 더욱 가속화 될 것으로 예상되어 우리 사회에서 대장암에 대한 적극적 관심과 연구가 반드시 필요하다. 또한 대장암은 완치 후 재발률이 최대 50%에 이를 정도로 높아 그 위험률은 더 심각하다. 대장암은 다양한 유전자 이상의 축적으로 발생하는 대표적인 질환이기 때문에 NGS 이용한 유전자변이 발굴이 대장암 바이오마커 개발로 이어져 실제 진단에도 활용되고 있다. TCGA(Pancancer Altals), MSKCC, DFCI 에서의 대규모 대장암 검체를 분석하여 다양한 유전자 이상을 보고 하고 있는데, 대표적으로 암유전자 변이 빈도율이 높은 유전자는 APC, TP53, KRAS, SMAD4, BRAF, PIK3CA, EGFR, ERBB2, NRAS, 및 PTEN 등이 보고된 바 있다. 또한, 대장암 환자 96~98%는 이런 고빈도 암유전자(들)에 돌연변이를 가지고 있다.
기존 유전자 변이를 분석하기 위한 방법으로는 마이크로어레이를 이용하여 유전자형을 확인해보는 microarray genotyping 방법이 이용되고 있다. 이는 작은 슬라이드 chip상에 수많은 합성 DNA 조각을 미세하게 집적시킨 올리고 뉴클레오티드 마이크로 어레이 (또는 마이크로 칩 (DNA chip))을 사용하여 분석한다. 분석하고자 하는 환자의 검체의 DNA 조각을 형광으로 표지한 후 DNA chip에 반응시키면 상보적인 서열로 이루어져 있는 올리고 뉴클레오티드(프로브)와 결합이 이루어지고, 이를 레이저 빛으로 스캔하면 분석이 가능하다. 마이크로어레이는 유전자의 돌연변이, 유전형 분석, 유전체 분석 등에서 활용되고 있으며 보통 SNP, indel, fusion 등을 보는데 이용된다. 하지만 이 방법은 인간의 실수로 인한 결과 해석의 모호함, 검출의 정확도가 높지 않다는 점 및 비교적 많은 DNA양이 필요하다는 한계점이 있다.
마이크로어레이와 함께 많이 사용되는 방법으로 PCR을 이용한 방법이 있다. 이는 타겟(target) 유전자 영역에 대하여 중합효소연쇄반응(PCR)을 통해 증폭하고, 이를 Sanger sequencing을 통하여 염기 서열을 분석하는 방법이다. 염기서열 분석하기 전에 타겟 영역을 모두 증폭해야 하므로 각 영역을 증폭하기 위한 프라이머 제작 비용, 다소 높은 비용의 sanger sequencing, 및 데이터의 낮은 커버리지, 데이터 쏠림 현상으로 인한 낮은 균일성으로 인하여 넓은 영역에 대하여 분석하는데 효율성이 낮은 등의 문제점이 있다. 또한 high-throughput 스크리닝 검사기술이 아니므로 효율적으로 원하는 부분을 선별할 수 없다.
최근에는 암의 발견을 위해 혈액속에 존재하는 세포유리 DNA (cell-free DNA, cfDNA)를 사용하고자 하는 노력이 있다. 건강한 사람들의 경우 조혈 세포 (haematopoietic cell)로부터 방출된 DNA가 대부분이다. 하지만 암 환자의 경우 cfDNA에는 암세포 사멸로 파괴된 세포로부터 혈액으로 방출된 순환 종양 DNA (circulating tumor DNA, ctDNA)가 포함되어 있다. 이 ctDNA는 특정 암과 관련된 유전적 변이를 포함하고 있으며, 이러한 유전적 변이의 모니터링을 통해, 병변 발생 전 암의 조기 발견, 특정 암치료법에 대한 반응 분석, 항암제에 대한 저항성 생성 기전 발견, 잔존 암의 존재 등의 확인이 가능하다.
대한민국 공개특허 2017-0014835호는 대장암 발병 진단 및 예측용 유전 마커를 개시한다. 프로브를 이용하여 특정 유전자의 염기서열을 확인함으로써 대장암 예후를 예측할 수 있는 조성물을 제공한다. 그러나 단일염기다형성(SNP)염기 확인을 목적으로 하고 있어, 넓은 타겟 영역에 대하여 염기서열 분석을 수행할 수 없으며, cfDNA의 시료를 사용한 차세대 염기서열 분석 기술 (next-generation sequencing, NGS) 에는 사용의 한계가 있다.
따라서 cfDNA와 같은 적은 양으로 존재하는 혈액의 DNA를 이용하여 다양한 여러 유전자에 걸쳐 존재하는 염기 서열 변이를 정확하고 신속하게 분석할 수 있는 NGS 기반의 타겟 시퀀싱 분석기술이 필요하다.
대장암의 다빈도 유전자 변이 탐색을 위한 차세대 염기서열 분석 (next-generation sequencing, NGS) 기술 기반 프로브 서열 및 조성물을 제공하고자 한다.
한 양태에서 본원은 대장암에서 다빈도로 나타나는 유전자 변이 탐색을 위해, 프로브 세트 및 그 용도를 제공한다.
본원에 따른 프로브 세트는 유전자 APC, TP53, KRAS, SMAD4, BRAF, PIK3CA, EGFR, ERBB2, NRAS 및 PTEN 을 타겟으로 하여 상기 각 유전자의 코딩 시퀀스, 즉 단백질을 코딩하는 엑손(exon)을 커버하도록 디자인된 프로브 세트를 제공한다.
일 구현예에서 본원에 따른 프로브 세트는, 대장암 환자로부터 분리된 혈액의 cfDNA 또는 대장암 환자로부터 분리된 대장암 조직의 유전체 DNA로부터 하기 각 유전자 캡처 또는 포획를 위한 서열번호 1 내지 서열번호 675의 핵산 서열로 표시되는 프로브를 포함한다:
Figure 112020122421468-pat00001
본원에 따른 프로브 세트가 사용되는 cfDNA는 ctDNA를 포함한다. 본원에 따른 프로브는 ctDNA의 상기 각 유전자에 결합 또는 혼성화하여, 상기 유전자를 캡처하고 이렇게 캡쳐된 DNA는 NGS 분석을 통해 서열이 결정되고, 서열변이가 검출된다. 대장암에서 나타나는 상기 각 유전자의 서열 변이는 대장암 진단, 대장암 재발여부를 확인, 또는 항암제에 대한 내성획득여부 판단에 사용될 수 있다. 상기 각 유전자에 대한 서열변이와 대장암과의 관련성은 알려진 것으로 당업자라면 연관시킬 수 있을 것이다.
이에 다른 양태에서 다른 양태에서 본원에 따른 프로브 세트를 포함하는 대장암 변이 다빈도 유전자 캡처용 조성물 또는 키트를 제공한다.
또 다른 양태에서 본원에 따른 프로브 세트를 포함하는, NGS 분석에 사용되는 대장암 진단에 필요한 유전자 캡처용 조성물 또는 키트를 제공한다.
또 다른 양태에서 본원은 본원에 따른 프로브 세트를 대장암의 진단이 필요한 환자의 혈액으로부터 추출된 cfDNA와 혼합하여, 상기 각 프로브가 상응하는 서열의 해당 유전자에 혼성화하는 단계를 포함하는, 본원에 따른 프로브 세트를 이용한 상기 각 유전자 캡쳐 방법을 제공한다.
본원에 따른 프로브를 사용하여 유전자는 NGS 분석에 사용된다.
NGS 분석에서 결정된 각 유전자의 서열에서 돌연변이를 검출하고, 상기 각 유전자의 서열변이는 대장암 재발여부를 확인, 또는 항암제에 대한 내성획득여부 판단에 사용될 수 있다.
다른 양태에서 본원에 따른 프로브 세트를 대장암의 진단 또는 경과 관찰이 필요한 환자의 혈액으로부터 추출된 cfDNA와 혼합하여, 상기 각 프로브가 상응하는 cfDNA 서열에 혼성화하도록 하여, 상기 각 유전자를 캡처하는 단계; 및 상기 캡쳐된 유전자에 대한 NGS 분석을 수행하는 단계를 포함하는, 대장암 진단 또는 경과 관찰에 필요한 정보를 제공하기 위해 대장암 환자의 상기 각 유전자 서열 결정 방법을 제공한다. 결정된 유전자 서열의 변이 여부를 확인 할 수 있다. 대장암에서 나타나는 상기 각 유전자의 서열변이는 대장암 재발여부를 확인, 또는 항암제에 대한 내성획득여부 판단에 사용될 수 있다. 상기 각 유전자에 대한 서열변이와 대장암과의 관련성은 알려진 것으로 당업자라면 연관시킬 수 있을 것이다.
기존의 유전자 변이 검사를 위한 타깃 시퀀싱 방법은 분석하고자 하는 영역을 중합효소연쇄반응(PCR) 과정을 통해 증폭하고 이를 차세대염기서열분석(NGS) 기술을 통하여 분석하였으나, 본원에 따른 프로브는, 유전자와 프로브 간의 혼성화(hybridization) 방법을 이용하여 특정 영역을 효율적으로 캡쳐한 후 차세대염기서열에 수행되며, 특히 본원에서는 프로브 디자인을 최적화 하여 유전자 타깃 영역에 대한 높은 커버리지, 높은 데이터 균일성, 데이터의 쏠림 현상 등을 월등히 개선시킬 수 있다.
본원에 따른 대장암의 다빈도 유전자 변이 탐색을 위한 특히 염기서열 분석 기반 프로브를 사용하는 경우, 프로브와 유전자 간의 혼성화 방법을 이용한 NGS 기반의 타겟 시퀀싱 방법으로, 기존의 microarray 방법이나 PCR 방법에 비해 많은 유전자의 보다 넓은 타겟 염기서열을 비교적 낮은 비용으로 정확하고 민감하며 높은 재현성으로 분석할 수 있다.
나아가 본원에 따른 프로브를 이용한 서열분석으로 특히 조직샘플이 없는 환자의 경우 대장 내시경을 통해 조직샘플을 얻는 불편한 과정이 없이도, 혈액 샘플을 통해 유전자 변이의 검출이 가능하여, 이를 이용하면 대장암 진단, 대장암 재발 여부를 확인할 수 있으며, 항암제에 대한 내성획득여부 등도 확인할 수 있다.
도 1은 본원의 한 구현예에 따른 프로브 디자인의 개념도이다.
도 2는 본원의 한 구현예에 따른 프로브를 이용해 캡쳐한 모습을 나타낸다.
도 3은 본원의 한 구현예에 따른 프로브를 디자인한 후 Rebalancing 설계를 위해 프로브를 디자인한 후 이를 표준물질을 이용하여 타깃 시퀀싱을 진행하여 캡쳐하고 그 결과를 분석한 데이터이다.
도 4는 AF 1% 표준물질을 프로브로 캡쳐한 후 변이의 VAF를 확인한 결과로 평균과 중앙값이 예상했던 1%와 유사하게 나오는 것을 확인한 결과이다 (표 14 참조).
본원의 대장암의 다빈도 돌연변이 유전자의 유전체 상의 변이 검출을 차세대 염기서열 분석 (next-generation sequencing, NGS)을 이용하여 측정하기 위한 프로브 세트 또는 조합 또는 패널 발견에 근거한 것이다.
구체적으로 본원은 대장암 환자에서 발견되는 다빈도 유전자 : APC, TP53, KRAS, SMAD4, BRAF, PIK3CA, EGFR ERBB2, NRAS, 및 PTEN 10개를 대상으로 상기 유전자 패널의 포획 패널로, 각 유전자 별로 각 유전자의 전체를 커버할 수 있는 수 십개의 프로브의 디자인하였다.
상기 각 유전자는 다음과 같이 서열이 공지되어 있다: APC(APC Regulator Of WNT Signaling Pathway; Entrez Gene ID: 324), TP53(Tumor Protein P53;Entrez Gene ID: 7157), KRAS(KRAS Proto-Oncogene, GTPase;Entrez Gene ID: 3845), SMAD4(SMAD Family Member 4;Entrez Gene ID: 4089), BRAF(B-Raf Proto-Oncogene, Serine/Threonine Kinase;Entrez Gene ID: 673), PIK3CA(Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha;Entrez Gene ID: 5290), EGFR(Epidermal Growth Factor Receptor;Entrez Gene ID: 1956), ERBB2(Erb-B2 Receptor Tyrosine Kinase 2;Entrez Gene ID: 2064), NRAS(NRAS Proto-Oncogene, GTPase;Entrez Gene ID: 4893), 및 PTEN(Phosphatase And Tensin Homolog;Entrez Gene ID: 5728).
이에 한 양태에서 본원은 APC, TP53, KRAS, SMAD4, BRAF, PIK3CA, EGFR ERBB2, NRAS, 및 PTEN로 구성되는 군으로부터 선택되는 하나 이상 유전자에 대하여 상기 각 유전자를 캡쳐할 수 있는 프로브 세트에 관한 것이며, 각 유전자에 대한 프로브 세트의 서열번호는 다음 표 1과 같다.
[표 1]
Figure 112020122421468-pat00002
일 구현예에서 본원에 따른 프로브 세트는 상기 모든 유전자를 캡처할 수 있는 프로브 세트를 포함한다.
본원에 따른 프로브 세트는 대장암의 다빈도 돌연변이 유전자의 유전체 상의 돌연변이 분석을 위해, 차세대 염기서열 분석 (next-generation sequencing, NGS)를 이용한 타켓 시퀀싱에 사용된다.
본원에서 “NGS (Next Generation Sequencing)”란, 유전체의 염기서열 분석기술 중 하나로, 유전체 유래의 DNA 단편을 병렬로 처리함으로써 염기서열을 고속으로 분석할 수 있다. 이를 위해 단편에 인덱스, 분자바코드 등을 추가하고 증폭하는 과정을 포함하는 라이브러리 제조 및 산출된 원(raw) 데이터의 정렬(alignment) 및 참조 염기서열에의 맵핑을 통한 오류 처리 및 염기서열 도출 등의 데이터 분석 과정이 필요하다. 차세대 염기서열 분석은 목적에 따라 다양한 분석 플랫폼으로 이용될 수 있다. 예를 들어, 차세대 염기서열 분석의 분석 플랫폼은 Illumina NextSeq, Illumina NovaSeq, ThermoFisher Ion Proton, Pacific Biosciences Sequel II, BGI MGI 등을 들 수 있고, 각 플랫폼에 사용되는 라이브러리 제조 키트 및 방법과 데이터 분석 프로그램은 해당 플랫폼 제조사로부터 입수할 수 있다.
본원에서 “타깃 시퀀싱”이란 전체 유전체(genome)에서 “목적하는 유전자의 DNA 서열 정보”를 알아내는 분석 방식이다. 이러한 타킷 시퀀싱에서는 목적하는 유전자 부위만을 포획 또는 캡쳐(capture)하는 타깃 캡쳐(target capture)가 필수적으로 선행되어야 하고, 이를 위해 프로브(probe)가 필요하다. 본원에 따른 프로브는 이러한 타깃 시퀀싱에 사용된다.
기존의 유전자 변이 검사를 위한 타깃 시퀀싱 방법은 분석하고자 하는 영역을 중합효소연쇄반응(PCR) 과정을 통해 증폭하고 이를 차세대염기서열분석(NGS) 기술을 통하여 분석하였으나, 본원에 따른 프로브는, 유전자와 프로브 간의 혼성화(hybridization) 방법을 이용하여 특정 영역을 효율적으로 캡쳐한 후 차세대염기서열을 수행하는데 사용되는 것이며, 특히 본원에서는 프로브 디자인을 최적화 하여 유전자 타깃 영역에 대한 높은 커버리지, 높은 데이터 균일성, 데이터의 쏠림 현상 등을 월등히 개선시킬 수 있다.
프로브는 약 200개 이하의 염기로 구성되는 단일가닥 올리고뉴클레오타이드로 통상적으로 올리고뉴클레오티드 합성기를 이용하여 DNA 형태로 화학적으로 합성된다. 프로브를 이용하여 유전체 DNA를 캡쳐하기 위해서는 이들간의 상보적인 결합력을 이용하게 되는데 상보적 결합력은 DNA-DNA, RNA-DNA, RNA-RNA 순으로 강해지므로 효율적인 타겟 캡쳐를 위해서 DNA 올리고뉴클레오티드의 형태로 합성된 프로브를 in vitro transcription을 통해 RNA 올리고뉴클레오티드의 형태(target capture RNA probe)로 제작한다. 이후 혼성화(hybridization) 과정을 통해 사용자가 원하는 유전체(genome)상의 특정 타겟 영역만을 프로브를 이용하여 캡쳐하여 분리한다. 이렇게 캡쳐된 영역은 NGS을 이용하여 유전자 변이를 확인할 수 있다. 유전자 변이는 유전자 카피수 변이 및 돌연 변이 (점 돌연변이, 삽입 또는 결실 돌연변이)를 포함하며, 공지된 NGS 데이터 분석시스템을 이용하여 검출할 수 있다.
본원에 따른 프로브는 특히 cfDNA 또는 ctDNA를 이용한 NGS 분석에 사용된다.
본원에서 “cfDNA(cell-free DNA, cfDNA)”는 혈액 속에 존재하는 다양한 길이의 유전체 단편을 포함하나, 히스톤 단백질에 의해 보호되지 않는 크로마틴 부분이 주로 잘려서 166 bp 길이에서 최빈값을 보인다. cfDNA는 건강한 사람들의 경우 조혈 세포(haematopoietic cell)로부터 방출된 DNA가 대부분이고, 암환자의 경우, 암세포 사멸로 인해 후술하는 바와 같이 암세포 유래의 ctDNA를 포함한다. cfDNA는 혈액으로부터 추출될 수 있으며, 이를 추출하는 시약/키트는 시중에서 구입할 수 있고, 그 방법은 공지되어 있다 (Clara Perez-Barrios et al. Traansl Lung Cancer Res 5 (2016).
본원에서 “ctDNA (circulating tumor DNA)”는 cfDNA에 포함된, 암세포에서 유래된 유전체 단편이다. 총 cfDNA의 단지 <0.1 ~ 10% 양으로 포함되어 있다. ctDNA는 암세포의 급격한 자기복제로 인해 히스톤 의해 보호되는 부위가 더 적고 결과적으로 건강한 세포유래 cfDNA보다 더 짧아져 주로 90 ~ 150 bp의 길이로 보통의 cfDNA보다 약 20-40 bp (Mouliere, F. et al. Sci Transl Med 10, (2018).) 짧다. 이러한 ctDNA는 특정 암과 관련된 유전적 변이를 포함하고 있어 혈액을 이용한 이러한 유전적 변이의 모니터링을 통해, 병변 발생 전 암의 조기 발견, 특정 암치료법에 대한 반응 분석, 항암제에 대한 저항성 생성 기전 발견, 잔존 암의 존재 등의 확인에 유용하게 사용될 수 있다. 본원에 따른 일 구현예에서는 cfDNA에 포함된 DNA 유전체 단편 중에서 약 1% 미만의 저빈도로 존재하는 암세포 유래의 ctDNA의 유전자 변이를 검출하고자 한다.
cfDNA 또는 ctDNA는 유전체(genome)에서 유래된 유전체의 단편으로, 하나의 유전자가 여러 개이 단편으로 나뉘어 존재할 수 있고, 이러한 하나의 유전자에 해당하는 모든 단편을 캡쳐하여, 목적하는 유전자의 전체에 걸쳐 존재하는 변이를 정확하게 알아내는 것이 필요하며, 본원에 따른 프로브 세트는 이를 달성할 수 있다.
본원에 따른 프로브 디자인은 타깃 시퀀싱을 위한 것으로, 프로브 디자인을 위해 먼저 특정 암과 관련된 유전자를 선정하고 이를 타겟으로 하여 해당 코딩 시퀀스(coding sequence), 즉 단백질로써 코딩되는 엑손으로 구성된 부분에 대한 DNA 시퀀스를 포함하도록 디자인하였다. 이때 목적하는 유전자의 전사체(transcript)를 모두 포함할 수 있도록 프로브를 디자인 하였다. 프로브는 타겟 영역의 모든 염기를 포함하고 타겟 영역 밖 수 bp 정도를 포함하도록 디자인하였다. 또한 모든 염기에 대하여 최소 2개 이상의 프로브가 겹치도록 하는 tiling 기법을 이용하여 디자인함으로써 모든 영역에 대하여 효율적으로 캡쳐 되도록 할 수 있다.
본원에 따른 프로브 시퀀스 디자인은 유전자 별로 재조합 된 시퀀스의 CDS 시작지점을 기준으로 참조 유전체(reference genome) 상에서 상부(upstream)쪽으로 일정 영역 (30-60bp) 확장하도록 디자인하여, 유전자 간(intergenic) 영역에서 프로브 시작 지점을 설정하였다. 이로부터 프로브의 길이에 따라 일정 부분이 다음 순서의 것과 겹치도록 프로브를 순차적으로 디자인하였다. 이때 이웃하는 프로브간에 약 60bp 정도씩 겹치도록 하는 2X tiling 기법으로 디자인함으로써 목적하는 유전자의 모든 영역이 효율적으로 캡쳐 되도록 할 수 있다. 또한 프로브의 on-target ratio 및 uniformity 향상을 위하여 타겟의 양 말단에서 시작하는 terminal 프로브를 추가로 디자인하였으며, 프로브가 타깃 유전자와 결합하는 위치에 높은 GC ratio를 지니거나 특정 서열이 반복적으로 나타났을 때 캡쳐 효율이 낮아질 수 있으므로 이를 보완하기 위하여 프로브 시퀀스를 조정하는 방법 (G 또는 C가 4개 이상 연속될 때에 4번째 base를 A 또는 T로 치환하는 GC fix 과정)을 적용하여 목적하는 유전자의 전 영역을 효율적으로 캡쳐 할 수 있도록 디자인하였다.
또한 본원에서는 프로브를 1차로 디자인한 후 이를 표준물질을 이용하여 NGS 타깃 시퀀싱을 진행하여 캡쳐 결과를 분석하여, 캡쳐가 잘 되지 않은 부분을 보완하는 rebalancing 과정을 수행하여 디자인된 것이다. NGS Normalized depth (Read depth)가 상대적으로 낮은 영역에 대해서는 동일한 프로브를 depth 수치에 따라 n배 추가로 삽입하는 과정이다. 캡쳐가 되지 않은 영역에 대해서는 타겟 시퀀스에 GC가 높거나 특정 서열 반복이 높아서 캡쳐가 되지 않았다고 판단하여 주변부로 프로브를 30bp 이동하여 디자인함으로써 캡쳐의 효율을 향상 시킬 수 있다.
본원에 따른 프로브 세트가 사용되는 cfDNA는 ctDNA를 포함한다. 본원에 따른 프로브는 ctDNA의 상기 각 유전자에 결합 또는 혼성화하여, 상기 유전자를 캡처하고 이렇게 캡쳐된 DNA는 NGS 분석을 통해 서열이 결정되고, 서열변이가 검출된다. 대장암에서 나타나는 상기 각 유전자의 서열변이는 대장암 재발여부를 확인, 또는 항암제에 대한 내성획득여부 판단에 사용될 수 있다.
이에 다른 양태에서 본원에 따른 프로브 세트를 포함하는 대장암 변이 다빈도 유전자 캡처용 조성물 또는 키트에 관한 것이다.
본원에 따른 프로브를 사용하여 유전자는 NGS 분석에 사용된다.
또 다른 양태에서 본원에 따른 프로브 세트를 포함하는, NGS 분석에 사용되는 대장암 진단에 필요한 유전자 캡처용 조성물 또는 키트에 관한 것이다.
NGS 분석에서 결정된 각 유전자의 서열에서 돌연변이를 검출하고, 상기 각 유전자의 서열변이는 대장암 진단, 대장암 재발여부를 확인, 또는 항암제에 대한 내성획득여부 판단 등에 사용될 수 있다.
다른 양태에서 본원에 따른 프로브 세트를 대장암의 진단 또는 경과 관찰이 필요한 환자의 혈액으로부터 추출된 cfDNA와 혼합하여, 상기 각 프로브가 상응하는 cfDNA 서열에 혼성화하도록 하여, 상기 각 유전자를 캡처하는 단계; 및 상기 캡쳐된 유전자에 대한 NGS 분석을 수행하는 단계를 포함하는, 대장암 진단 또는 경과 관찰에 필요한 정보를 제공하기 위해 대장암 환자의 상기 각 유전자 서열 결정 방법을 제공한다. 결정된 유전자 서열의 변이 검출은 생성된 파일과 참조 유전체 사이의 서열 차이점을 비교하여 검출한다. 이때 NGS에서 생성된 BAM (Binary Alignment/Map format File) 이 사용될 수 있다. 검출된 변이는 VCF 형식을 이용하여 저장된다. 변이 검출에 사용되는 검출기 (소프트웨어)는 공지되어 있으며 예를 들면 Metect2 (Broad Institue), LoFreq(Genome Institue of Singapore), 또는 Delly2(European Molecular Biology Laboratory (EMBL))이 사용될 수 있다.
대장암에서 나타나는 상기 각 유전자의 서열 변이는 대장암 재발여부를 확인, 또는 항암제에 대한 내성획득여부 판단에 사용될 수 있다. 상기 각 유전자에 대한 서열변이와 대장암과의 관련성은 알려진 것으로 당업자라면 연관시킬 수 있을 것이다.
실시예
실시예 1. 유전자 선정
표 2에 기재된 대장암 환자에서 발견되는 다빈도 유전자 (APC, TP53, KRAS, SMAD4, BRAF, PIK3CA, EGFR ERBB2, NRAS, 및 PTEN ) 10개를 대상으로 유전자 패널 포획 패널을 디자인하여 실시예 2에 기재된 방법대로 서열번호 1 내지 675의 서열로 표시되는 프로브를 디자인 하였다.
[표 2]
Figure 112020122421468-pat00003
실시예 2. 프로브 (Probe) 디자인
프로브 디자인을 하기 위해 타깃 영역을 확인하였다. 타깃 시퀀싱을 위한 프로브 디자인은 먼저 특정 암과 관련된 유전자를 선정하였고 이들을 타깃으로 하여 해당 코딩 시퀀스, 즉 단백질로써 코딩 되는 exon으로 구성된 부분에 대한 DNA 시퀀스를 포함하도록 디자인하였다.
프로브 시퀀스 디자인 설계는 도 1의 모식도와 같이 수행하였다. 10개 유전자 별로 재조합 된 시퀀스의 CDS 시작지점을 기준으로 reference genome 상에서 upstream쪽으로 일정 영역 (30-60bp) 확장하여 intergenic 영역에서 프로브 시작 지점을 설정하였다. 이로부터 프로브의 길이에 따라 일정 부분이 다음 순서의 것과 겹치도록 프로브를 순차적으로 디자인 설계를 수행하였다. 이때 이웃하는 프로브간에 60bp정도씩 겹치도록 하는 2X tiling 기법으로 디자인함으로써 모든 영역에 대하여 캡쳐하였다. 프로브의 on-target ratio 및 uniformity 향상을 위하여 타겟의 양 말단에서 시작하는 terminal 프로브를 추가 디자인하였으며, 프로브가 타겟 유전자와 결합하는 위치에 높은 GC ratio를 지니거나 특정 서열이 반복적으로 나타났을 때 캡쳐 효율이 낮아질 수 있으므로 이를 보완하기 위하여 프로브 시퀀스를 조정하는 방법 (G 또는 C가 4개 이상 연속될 때에 4번째 base를 A 또는 T로 치환하는 GC fix과정)을 적용하여 캡쳐를 수행하였다.
Rebalancing 설계를 위해 프로브를 1차로 디자인한 후 이를 표준물질을 이용하여 타깃 시퀀싱을 진행하여 캡쳐하였다. 표준물질로는 3개 (NA12878, NA12891, NA12892)를 프로브를 이용해 캡쳐하였다. NGS 분석은 셀레믹스 분석 파이프라인을 사용하였다. 각각의 샘플은 다음 과정으로 분석했다. Trimmomatic 프로그램을 사용해 fastq 파일의 adapter 서열을 제거했다. 그리고 BWA를 이용해 hg19 참조 유전체에 mapping해서 bam 파일을 만들었다. Bam 파일은 picard를 이용해 유전체 위치 순서로 정렬했다. 그리고 PCR duplicates를 picard 를 이용해 제거했다. 그리고 GATK 를 사용해 INDEL realignment를 진행하고, base quality recalibration을 진행했다. 이후 samtools를 사용해 mapping quality가 낮은 reads를 제거했다. Varaint는 VarScan을 이용해 찾았다.
NGS 결과를 도 2와 같이 분석하여, 캡쳐가 잘 되지 않은 부분을 보완하기 위한 rebalancing 과정을 진행하였다. 캡쳐가 되지 않은 영역에 대해서는 타겟 시퀀스에 GC가 높거나 특정 서열 반복이 높아서 캡쳐가 되지 않았다고 판단하여 주변부로 프로브를 30bp 이동하여 다시 디자인함으로써 다음 표 3과 같이 캡쳐의 효율을 향상시켰다.
[표 3]
Figure 112020122421468-pat00004
Rebalancing 후 0.2x와 0.5x의 mean depth coverage uniformity가 크게 향상되었다 (표 5). 이 수치가 증가하는 것은 평균적인 depth와 차이나는 부분 중 캡쳐가 잘 안되는 부분이 줄어드는 것을 의미하는 것이다. 0.2x mean depth coverage uniformity는 mean depth의 20%에 해당하는 depth를 만족하는 target 영역의 비율을 나타낸다. 0.5x mean depth coverage uniformity는 mean depth의 50%에 해당하는 depth를 만족하는 target 영역의 비율을 나타낸다.
상기와 같이 Rebalancing 과정을 통해 디자인된 프로브는 각 유전자 별로 서열번호 1 내지 서열번호 675로 나타냈다.
실시예 3. 본원에 따라 디자인된 프로브 패널을 이용한 패널 시퀀싱 결과
상기 실시예에 따라 제작한 대장암 맞춤형 유전자 포획 패널의 포획 성능을 확인하기 위하여 표준 gDNA 샘플 8개 (표 4 참조)에 대하여 본 출원인 제품인AlphaLiquid Colon® 시약을 제조사의 방법대로 사용하여 유전자 포획 (캡쳐) 실험을 진행하고 Illumina NextSeq550Dx 장비를 이용하여 시퀀싱 후 분석을 수행하였다. 실험에 사용한 cfDNA는 SeraseqTM ctDNA mutation mix v2 및 SeraseqTM cfDNA mutation mix v2 WT (SeraCare, Milford, MA)에서 구입하여 사용하였다. 실험 디자인은 다음 표 3과 같다. 시퀀싱 완료된 데이터를 입력 받아 다음과 같이 유전체분석을 진행하였다. 구체적으로 분석은 demultiplexing, mapping, denoising, variant call, 및 annotation 단계로 진행되었다. 참조 유전체로는 hg38을 사용하고, annotation 단계에는 dbSNP(build 151), ClinVar(2019-07), COSMIC(v89), 및 gnomAD(v2)가 사용되었다.
[표 4]
Figure 112020122421468-pat00005
그 결과는 도 3 및 표 5에 기재되어있다. 또한 표준 gDNA(genomic DNA) 샘플 8개 각각의 검사 결과는 표 6 ~ 13에 기재되어있다. 시퀀싱 데이터는 어댑터 서열이 있는 경우 어댑터 서열을 잘라내고, 표준 염기서열 (reference genome, GRCh37 - hg19)에 맵핑하여 alignment 정보를 담은 BAM 파일을 생성하였다. 분석 결과 유전자 포획 성능을 평가할 수 있는 Mapping ratio나 On-target ratio, 표적 영역에 대한 coverage 지표가 모두 우수한 것으로 나타났으며, 이는 본원의 제작한 대장암 맞춤형 유전자 포획 패널이 우수한 것으로 판단된다. Variant caller를 사용하여 BAM 파일에서 돌연변이를 분석하였으며, 표준물질로 검증된 돌연변이에 대해서 민감도 및 특이도 일치도를 확인하였다. 또한 대립유전자 빈도(Variant Allele Frequency, VAF) 1%인 표준물질에 대하여 민감도 99%, 특이도 99%, 일치도 100% 확인 되었다 .
[표 5]
Figure 112020122421468-pat00006
[표 6]
Figure 112020122421468-pat00007
[표 7]
Figure 112020122421468-pat00008
[표 8]
Figure 112020122421468-pat00009
[표 9]
Figure 112020122421468-pat00010
[표 10]
Figure 112020122421468-pat00011
[표 11]
Figure 112020122421468-pat00012
[표 12]
Figure 112020122421468-pat00013
[표 13]
Figure 112020122421468-pat00014
표 5에서 Input DNA: 실험에 사용한 DNA 양, Reference Material: 표준물질, Raw reads (개): 시퀀싱한 reads 개수, Sequencing Throughput (bp): 시퀀싱한 base pair 수, 0.2x mean depth coverage uniformity: mean depth의 20%에 해당하는 depth를 만족하는 target 영역의 비율, TP: True positive 개수, FP: False positive 개수, TN: True negative 개수, FN: False negative 개수, Sensitivity: 민감도, Specificity: 특이도. 표 6 내지 표 13에서 VAF: Variable Allele Frequency, CDS: Coding Sequence, ALT: Alternate Allele(s), 변이검출 파일 포맷 VCF(참조 유전체와 비교하여 다르다고 판단되는 변이와 그 빈도를 표시하는 표준형식의 파일 포맷)의 구성.
1% 표준물질에 대해 검출된 변이의 VAF는 평균적으로 1% 에 근사한 값이 측정되었다 (도 4, 표 14).
[표 14]
Figure 112020122421468-pat00015
실시예 4. 대장암 환자를 대상으로 한 본원에 따라 디자인된 프로브 패널을 이용한 분석결과
대장암 환자 5명을 대상으로 암조직과 cfDNA를 이용하여 본원에 따른 패널을 이용한 10개 유전자에 대한 패널 시퀀싱을 수행하여 조직 및 cfDNA의 돌연변이 가 100% 일치되는 것을 확인하였다 (표 15 참조). 즉 대장암조직에서 발견되는 모든 유전자의 돌연변이가 cfDNA에서 검출되는 것을 확인 하였다. 이는 본원에 따른 프로브를 사용한 방법이 재발을 포함하는 대장암 진단, 감시진단 및 모니터링 등에 효과적으로 사용될 수 있음을 나타낸다.
Tissue로부터 NGS로 확인된 돌연변이와 동일한 돌연변이가 cfDNA에서도 확인되었다. 병기나 암치료 과정에 따라 혈액속의 ctDNA 농도는 크게 차이가 나고 ctDNA의 농도에 비례하여 VAF 값이 달라진다. 특히 환자 4번, 5번의 경우 cfDNA에서 VAF 1% 이하의 변이도 검출했다. 일반적인 NGS 방법에서는 확인할 수 없었던 낮은 VAF에서의 민감도를 확인할 수 있었다.
[표 15]
Figure 112020122421468-pat00016
본원에 따른 대장암의 다빈도 유전자 변이 탐색을 위한 염기서열 분석 기반 프로브 서열 및 조성물은 차세대 염기서열 분석 기술과 타겟 캡쳐 기술을 기반으로 하여 여러 암종의 유전자 변이를 분석하기 위하여 효과적인 데이터 생성 방법을 위해 사용될 수 있는 프로브 디자인 최적화 기술이다.
<110> Seoul National University R&DB Foundation IMB Dx, Inc. <120> Probe Set for the Detection of High Frequency Gene Mutations related to Colorectal Cancer using Next-Generation Sequencing System <130> DP202006003P <150> KR 10-2019-0145804 <151> 2019-11-14 <160> 675 <170> KoPatentIn 3.0 <210> 1 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 1_NRAS <400> 1 ataagtgaca cattcagagt ataagaaaaa caaatataca aaattaacag gaatgagaat 60 acatttccaa acttgtccta ccttgaaagt ggctcttttc tgacaaaact ttaaaagtat 120 120 <210> 2 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 2_NRAS <400> 2 cttgaaagtg gctcttttct gacaaaactt taaaagtatc tgtaaaaaaa gaacagaaac 60 catgtcctta ttaactagtt tcaaagtagt gatccttcaa attcctggtc attgccagga 120 120 <210> 3 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 3_NRAS <400> 3 ccaaattgcc caatactata tactaagatt tgtaattatg ccaagaaacc atatgctcac 60 cttgttacat caccacacat ggcaatccca tacaaccctg agtcccatca tcactgctgt 120 120 <210> 4 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 4_NRAS <400> 4 cttgttacat caccacacat ggcaatccca tacaaccctg agtcccatca tcactgctgt 60 tgagtttttt cattcggtac tggcgtattt ctcttaccag tgtgtaaaaa gcatcttcaa 120 120 <210> 5 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 5_NRAS <400> 5 tgagtttttt cattcggtac tggcgtattt ctcttaccag tgtgtaaaaa gcatcttcaa 60 caccctataa aaggaaaaaa tgaaaaaaaa tgagagagct agctcaacgg acacaatcca 120 120 <210> 6 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 6_NRAS <400> 6 caccctataa aaggaaaaaa tgaaaaaaaa tgagagagct agctcaacgg acacaatcca 60 aattataagc tctcttgcat ttgtatctct ttatgtggac ataagattcc aattactaaa 120 120 <210> 7 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 7_NRAS <400> 7 tctaccagag ttaatcaact gatgcaaact cttgcacaaa tgctgaaagc tgtaccatac 60 ctgtctggtc ttggctgagg tttcaatgaa tggaatcccg taactcttgg ccagttcgtg 120 120 <210> 8 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 8_NRAS <400> 8 ctgtctggtc ttggctgagg tttcaatgaa tggaatcccg taactcttgg ccagttcgtg 60 ggcttgtttt gtatcaactg tccttgttgg caaatcacac ttgtttccca ctagcaccat 120 120 <210> 9 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 9_NRAS <400> 9 ggcttgtttt gtatcaactg tccttgttgg caaatcacac ttgtttccca ctagcaccat 60 aggtacatca tccgagtctt ttactcgctt aatctgctcc ctaaaaacgg gaatatatta 120 120 <210> 10 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 10_NRAS <400> 10 aggtacatca tccgagtctt ttactcgctt aatctgctcc ctaaaaacgg gaatatatta 60 tcagaacata agaaaaacaa gattaggctg ggtacagtgg ctcatgcctg caatctcagc 120 120 <210> 11 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 11_NRAS <400> 11 tccccataaa gattcagaac acaaagatca tcctttcaga gaaaataatg ctcctagtac 60 ctgtagaggt taatatccgc aaatgacttg ctattattga tggcaaatac acagaggaag 120 120 <210> 12 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 12_NRAS <400> 12 ctgtagaggt taatatccgc aaatgacttg ctattattga tggcaaatac acagaggaag 60 ccttcgcctg tcctcatgta ttggtctctc atggcactgt actcttcttg tccagctgta 120 120 <210> 13 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 13_NRAS <400> 13 ccttcgcctg tcctcatgta ttggtctctc atggcactgt actcttcttg tccagctgta 60 tccagtatgt ccaacaaaca ggtttcacca tctataacca cttgttttct gtaagaatcc 120 120 <210> 14 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 14_NRAS <400> 14 tccagtatgt ccaacaaaca ggtttcacca tctataacca cttgttttct gtaagaatcc 60 tgggggtgtg gagggtaagg gggcagggag ggagggaagt tcaattttta ttaaaaacca 120 120 <210> 15 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 15_NRAS <400> 15 taaagatgat ccgacaagtg agagacagga tcaggtcagc gggctaccac tgggcctcac 60 ctctatggtg ggatcatatt catctacaaa gtggttctgg attagctgga ttgtcagtgc 120 120 <210> 16 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 16_NRAS <400> 16 ctctatggtg ggatcatatt catctacaaa gtggttctgg attagctgga ttgtcagtgc 60 gcttttccca acaccacctg ctccaaccac caccagtttg tactcagtca tttcacacca 120 120 <210> 17 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 17_NRAS <400> 17 gcttttccca acaccacctg ctccaaccac caccagtttg tactcagtca tttcacacca 60 gcaagaacct gttggaaacc agtaatcagg gttaattggc gagccacatc tacagtactt 120 120 <210> 18 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 18_NRAS <400> 18 gcaagaacct gttggaaacc agtaatcagg gttaattggc gagccacatc tacagtactt 60 taaagctttc tataatcaat ggaaatgaaa accctagtgt gaccttccat ttggttctta 120 120 <210> 19 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 19_PIK3CA <400> 19 ataaatgtat tcttctgtag ttgtgtctct tttaacatat gttttccttc tttgatttag 60 gtttctgctt tgggacaacc atacatctaa ttccttaaag tagttttata tgtaaaactt 120 120 <210> 20 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 20_PIK3CA <400> 20 gtttctgctt tgggacaacc atacatctaa ttccttaaag tagttttata tgtaaaactt 60 gcaaagaatc agaacaatgc ctccacgacc atcatcaggt gaactgtggg gcatccactt 120 120 <210> 21 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 21_PIK3CA <400> 21 gcaaagaatc agaacaatgc ctccacgacc atcatcaggt gaactgtggg gcatccactt 60 gatgccccca agaatcctag tagaatgttt actaccaaat ggaatgatag tgactttaga 120 120 <210> 22 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 22_PIK3CA <400> 22 gatgccccca agaatcctag tagaatgttt actaccaaat ggaatgatag tgactttaga 60 atgcctccgt gaggctacat taataaccat aaagcatgaa ctatttaaag aagcaagaaa 120 120 <210> 23 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 23_PIK3CA <400> 23 atgcctccgt gaggctacat taataaccat aaagcatgaa ctatttaaag aagcaagaaa 60 ataccccctc catcaacttc ttcaagatga atcttcttac attttcgtaa gtgttactca 120 120 <210> 24 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 24_PIK3CA <400> 24 ataccccctc catcaacttc ttcaagatga atcttcttac attttcgtaa gtgttactca 60 agaagcagaa agggaagaat tttttgatga aacaagacga ctttgtgacc ttcggctttt 120 120 <210> 25 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 25_PIK3CA <400> 25 agaagcagaa agggaagaat tttttgatga aacaagacga ctttgtgacc ttcggctttt 60 tcaacccttt ttaaaagtaa ttgaaccagt aggcaaccgt gaagaaaaga tcctcaatcg 120 120 <210> 26 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 26_PIK3CA <400> 26 tcaacccttt ttaaaagtaa ttgaaccagt aggcaaccgt gaagaaaaga tcctcaatcg 60 agaaattggt atgatacaat atcctattct aaaatgcaaa taaccataaa gcttaactgt 120 120 <210> 27 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 27_PIK3CA <400> 27 agaaattggt atgatacaat atcctattct aaaatgcaaa taaccataaa gcttaactgt 60 tgtccctttc taaaatattt ctgtctaaac caataccttc gtaatcttaa atagctttct 120 120 <210> 28 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 28_PIK3CA <400> 28 aaacatgttc atgctgtgta tgtaatagaa tgttatattc tttatgtaat tttattaaag 60 gttttgctat cggcatgcca gtgtgtgaat ttgatatggt taaagatcca gaagtacagg 120 120 <210> 29 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 29_PIK3CA <400> 29 gttttgctat cggcatgcca gtgtgtgaat ttgatatggt taaagatcca gaagtacagg 60 acttccgaag aaatattctg aacgtttgta aagaagctgt ggatcttagg gacctcaatt 120 120 <210> 30 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 30_PIK3CA <400> 30 acttccgaag aaatattctg aacgtttgta aagaagctgt ggatcttagg gacctcaatt 60 cacctcatag tagagcaatg tatgtctatc ctccaaatgt agaatcttca ccagaattgc 120 120 <210> 31 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 31_PIK3CA <400> 31 cacctcatag tagagcaatg tatgtctatc ctccaaatgt agaatcttca ccagaattgc 60 caaagcacat atataataaa ttagataaag gtaagaaaat gactaatcta ctctaatcat 120 120 <210> 32 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 32_PIK3CA <400> 32 caaagcacat atataataaa ttagataaag gtaagaaaat gactaatcta ctctaatcat 60 tactatagtg cagtcttcta cctgtgtcta tatctttgta tagtcttttt ttttttttcc 120 120 <210> 33 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 33_PIK3CA <400> 33 atttctccct tgaaaaatga aagagagatg gtgattgcat ctaatgtttt cctgttatag 60 ggcaaataat agtggtgatc tgggtaatag tttctccaaa taatgacaag cagaagtata 120 120 <210> 34 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 34_PIK3CA <400> 34 ggcaaataat agtggtgatc tgggtaatag tttctccaaa taatgacaag cagaagtata 60 ctctgaaaat caaccatgac tgtgtaccag aacaagtaat tgctgaagca atcaggaaaa 120 120 <210> 35 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 35_PIK3CA <400> 35 ctctgaaaat caaccatgac tgtgtaccag aacaagtaat tgctgaagca atcaggaaaa 60 aaactcgaag tatgttgcta tcctctgaac aactaaaact ctgtgtttta gaatatcagg 120 120 <210> 36 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 36_PIK3CA <400> 36 aaactcgaag tatgttgcta tcctctgaac aactaaaact ctgtgtttta gaatatcagg 60 gcaagtatat tttaaaagtg tgtggatgtg atgaatactt cctagaaaaa tatcctctga 120 120 <210> 37 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 37_PIK3CA <400> 37 gcaagtatat tttaaaagtg tgtggatgtg atgaatactt cctagaaaaa tatcctctga 60 gtcagtataa ggtgagtaac aagtttcaaa atattaattt ttaatttaaa aagtaatcac 120 120 <210> 38 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 38_PIK3CA <400> 38 gtcagtataa ggtgagtaac aagtttcaaa atattaattt ttaatttaaa aagtaatcac 60 attgaggatg agtatctgta tttttttttt ttttttgaga cggaatctca ctctcgccca 120 120 <210> 39 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 39_PIK3CA <400> 39 atgttacttt taaaatgaaa aaccttacag gaaatggctc gcccccttaa tctcttacag 60 tatataagaa gctgtataat gcttgggagg atgcccaatt tgatgttgat ggctaaagaa 120 120 <210> 40 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 40_PIK3CA <400> 40 tatataagaa gctgtataat gcttgggagg atgcccaatt tgatgttgat ggctaaagaa 60 agcctttatt ctcaactgcc aatggactgt tttacaatgc catcttattc cagacgcatt 120 120 <210> 41 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 41_PIK3CA <400> 41 agcctttatt ctcaactgcc aatggactgt tttacaatgc catcttattc cagacgcatt 60 tccacagcta caccatatat gaatggagaa acatctacaa aatccctttg ggttataaat 120 120 <210> 42 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 42_PIK3CA <400> 42 tccacagcta caccatatat gaatggagaa acatctacaa aatccctttg ggttataaat 60 agtgcactca gaataaaaat tctttgtgca acctacgtga atgtaaatat tcgagacatt 120 120 <210> 43 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 43_PIK3CA <400> 43 agtgcactca gaataaaaat tctttgtgca acctacgtga atgtaaatat tcgagacatt 60 gataaggtaa agtcaaatgc tgatgcttat tattttatag aaattatttt agataacctt 120 120 <210> 44 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 44_PIK3CA <400> 44 gataaggtaa agtcaaatgc tgatgcttat tattttatag aaattatttt agataacctt 60 tttcttgcac tatacagtaa tctgttgacc tgtagtatgt tttcagatgg ttaggagaac 120 120 <210> 45 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 45_PIK3CA <400> 45 tatacattag tatataccta cttttttctt ttagatctat gttcgaacag gtatctacca 60 tggaggagaa cccttatgtg acaatgtgaa cactcaaaga gtaccttgtt ccaatcccag 120 120 <210> 46 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 46_PIK3CA <400> 46 atctatgttc gaacaggtat ctaccatgga ggagaaccct tatgtgacaa tgtgaacact 60 caaagagtac cttgttccaa tcccaggtaa ggaagtatat agatttatat ttccaaaggt 120 120 <210> 47 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 47_PIK3CA <400> 47 aaaattttac ataggtggaa tgaatggctg aattatgata tatacattcc tgatcttcct 60 cgtgctgctc gactttgcct ttccatttgc tctgttaaag gccgaaaggg tgctaaagag 120 120 <210> 48 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 48_PIK3CA <400> 48 gtggaatgaa tggctgaatt atgatatata cattcctgat cttcctcgtg ctgctcgact 60 ttgcctttcc atttgctctg ttaaaggccg aaagggtgct aaagaggtaa agtatttcag 120 120 <210> 49 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 49_PIK3CA <400> 49 aagtgttttg aaatgtgttt tataatttag actagtgaat atttttcttt gttttttaag 60 gaacactgtc cattggcatg gggaaatata aacttgtttg attacacaga cactctagta 120 120 <210> 50 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 50_PIK3CA <400> 50 gaacactgtc cattggcatg gggaaatata aacttgtttg attacacaga cactctagta 60 tctggaaaaa tggctttgaa tctttggcca gtacctcatg gattagaaga tttgctgaac 120 120 <210> 51 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 51_PIK3CA <400> 51 tctggaaaaa tggctttgaa tctttggcca gtacctcatg gattagaaga tttgctgaac 60 cctattggtg ttactggatc aaatccaaat aaagtaaggt ttttattgtc ataaattaga 120 120 <210> 52 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 52_PIK3CA <400> 52 cctattggtg ttactggatc aaatccaaat aaagtaaggt ttttattgtc ataaattaga 60 tattttttat ggcagtcaaa ccttctctct tatgtatata taatagcttt tcttccatct 120 120 <210> 53 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 53_PIK3CA <400> 53 tttatggcag tcaaaccttc tctcttatgt atatataata gcttttcttc catctcttag 60 gaaactccat gcttagagtt ggagtttgac tggttcagca gtgtggtaaa gttcccagat 120 120 <210> 54 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 54_PIK3CA <400> 54 gaaactccat gcttagagtt ggagtttgac tggttcagca gtgtggtaaa gttcccagat 60 atgtcagtga ttgaagagca tgccaattgg tctgtatccc gagaagcagg atttagctat 120 120 <210> 55 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 55_PIK3CA <400> 55 atgtcagtga ttgaagagca tgccaattgg tctgtatccc gagaagcagg atttagctat 60 tcccacgcag gactggtaag gcaaatcact gagtttatta agtatcaatt ataatctgtg 120 120 <210> 56 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 56_PIK3CA <400> 56 tcccacgcag gactggtaag gcaaatcact gagtttatta agtatcaatt ataatctgtg 60 gatttaggta gatactttct ctatggaaaa ggatccatat attttactgg catagatact 120 120 <210> 57 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 57_PIK3CA <400> 57 gaatccagag gggaaaaata tgacaaagaa agctatataa gatattattt tattttacag 60 agtaacagac tagctagaga caatgaatta agggaaaatg acaaagaaca gctcaaagca 120 120 <210> 58 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 58_PIK3CA <400> 58 agtaacagac tagctagaga caatgaatta agggaaaatg acaaagaaca gctcaaagca 60 atttctacac gagatcctct ctctgaaatc actgagcagg agaaagattt tctatggagt 120 120 <210> 59 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 59_PIK3CA <400> 59 atttctacac gagatcctct ctctgaaatc actgagcagg agaaagattt tctatggagt 60 cacaggtaag tgctaaaatg gagattctct gtttcttttt ctttattaca gaaaaaataa 120 120 <210> 60 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 60_PIK3CA <400> 60 cacaggtaag tgctaaaatg gagattctct gtttcttttt ctttattaca gaaaaaataa 60 ctgaatttgg ctgatctcag catgttttta ccatacctat tggaataaat aaagcagaat 120 120 <210> 61 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 61_PIK3CA <400> 61 gcaagaatgt ttatgtttat tttgtttctc ccacacagac actattgtgt aactatcccc 60 gaaattctac ccaaattgct tctgtctgtt aaatggaatt ctagagatga agtagcccag 120 120 <210> 62 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 62_PIK3CA <400> 62 acactattgt gtaactatcc ccgaaattct acccaaattg cttctgtctg ttaaatggaa 60 ttctagagat gaagtagccc aggtaaatgt atgtttgaga ttactagata actgttgtac 120 120 <210> 63 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 63_PIK3CA <400> 63 tggctcattc acaactatct ttccccttta aatatgattt attgtctttc tcatacacag 60 atgtattgct tggtaaaaga ttggcctcca atcaaacctg aacaggctat ggaacttctg 120 120 <210> 64 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 64_PIK3CA <400> 64 atgtattgct tggtaaaaga ttggcctcca atcaaacctg aacaggctat ggaacttctg 60 gactgtaatt acccagatcc tatggttcga ggttttgctg ttcggtgctt ggaaaaatat 120 120 <210> 65 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 65_PIK3CA <400> 65 gactgtaatt acccagatcc tatggttcga ggttttgctg ttcggtgctt ggaaaaatat 60 ttaacagatg acaaactttc tcagtattta attcagctag tacaggtaaa ataatgtaaa 120 120 <210> 66 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 66_PIK3CA <400> 66 ttaacagatg acaaactttc tcagtattta attcagctag tacaggtaaa ataatgtaaa 60 atagtaaata atgtttaatt acaataataa tttattctag atccatacaa cttcctttta 120 120 <210> 67 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 67_PIK3CA <400> 67 ttttggaatc acctaggtcc taaaatatga acaatatttg gataacttgc ttgtgagatt 60 tttactgaag aaagcattga ctaatcaaag gattgggcac tttttctttt ggcatttaaa 120 120 <210> 68 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 68_PIK3CA <400> 68 gtcctaaaat atgaacaata tttggataac ttgcttgtga gatttttact gaagaaagca 60 ttgactaatc aaaggattgg gcactttttc ttttggcatt taaagtaagt ctaattattt 120 120 <210> 69 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 69_PIK3CA <400> 69 tatttgtata ctgatttaag actatatata tatattttta attttgcacg attcttttag 60 atctgagatg cacaataaaa cagttagcca gaggtttggc ctgcttttgg agtcctattg 120 120 <210> 70 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 70_PIK3CA <400> 70 atctgagatg cacaataaaa cagttagcca gaggtttggc ctgcttttgg agtcctattg 60 tcgtgcatgt gggatgtatt tgaagcacct gaataggcaa gtcgaggcaa tggaaaagct 120 120 <210> 71 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 71_PIK3CA <400> 71 tcgtgcatgt gggatgtatt tgaagcacct gaataggcaa gtcgaggcaa tggaaaagct 60 cattaactta actgacattc tcaaacagga gaagaaggat gaaacacaaa aggtgtgtga 120 120 <210> 72 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 72_PIK3CA <400> 72 cattaactta actgacattc tcaaacagga gaagaaggat gaaacacaaa aggtgtgtga 60 ctctagtttg tgtttgagac tcttttcact gcagtggggc agagttgttt agaagcccag 120 120 <210> 73 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 73_PIK3CA <400> 73 tttttttaat caggtacaga tgaagttttt agttgagcaa atgaggcgac cagatttcat 60 ggatgctcta cagggctttc tgtctcctct aaaccctgct catcaactag gaaacctcag 120 120 <210> 74 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 74_PIK3CA <400> 74 gtacagatga agtttttagt tgagcaaatg aggcgaccag atttcatgga tgctctacag 60 ggctttctgt ctcctctaaa ccctgctcat caactaggaa acctcaggta ctttcttggg 120 120 <210> 75 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 75_PIK3CA <400> 75 tttcagggta aaataataat aaagcaaagg tacctagtaa agtttttaac tattttaaag 60 gcttgaagag tgtcgaatta tgtcctctgc aaaaaggcca ctgtggttga attgggagaa 120 120 <210> 76 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 76_PIK3CA <400> 76 gcttgaagag tgtcgaatta tgtcctctgc aaaaaggcca ctgtggttga attgggagaa 60 cccagacatc atgtcagagt tactgtttca gaacaatgag atcatcttta aaaatgggga 120 120 <210> 77 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 77_PIK3CA <400> 77 cccagacatc atgtcagagt tactgtttca gaacaatgag atcatcttta aaaatgggga 60 tggtaaggaa gagtattaat gagcttatga tgcatgaatt tagctatctt tttatacaca 120 120 <210> 78 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 78_PIK3CA <400> 78 tggtaaggaa gagtattaat gagcttatga tgcatgaatt tagctatctt tttatacaca 60 ggatatttat gaaccatgaa aactactgaa agccatttaa ggaatataca catgtgataa 120 120 <210> 79 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 79_PIK3CA <400> 79 tctgtggcat taaatggtga tacatattat ttgaatttca gatttacggc aagatatgct 60 aacacttcaa attattcgta ttatggaaaa tatctggcaa aatcaaggtc ttgatcttcg 120 120 <210> 80 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 80_PIK3CA <400> 80 atttacggca agatatgcta acacttcaaa ttattcgtat tatggaaaat atctggcaaa 60 atcaaggtct tgatcttcgg taggtaacca gtaaggcaac ctgtatgttg aaagttatcc 120 120 <210> 81 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 81_PIK3CA <400> 81 aaaacatttg ctattttaaa attccatcat ttaattgtaa acgtgttact cctctttcag 60 aatgttacct tatggttgtc tgtcaatcgg tgactgtgtg ggacttattg aggtggtgcg 120 120 <210> 82 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 82_PIK3CA <400> 82 aatgttacct tatggttgtc tgtcaatcgg tgactgtgtg ggacttattg aggtggtgcg 60 aaattctcac actattatgc aaattcagtg caaaggcggc ttgaaaggtg cactgcagtt 120 120 <210> 83 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 83_PIK3CA <400> 83 aaattctcac actattatgc aaattcagtg caaaggcggc ttgaaaggtg cactgcagtt 60 caacagccac acactacatc agtggctcaa agacaagaac aaaggagaaa tgtgagttgt 120 120 <210> 84 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 84_PIK3CA <400> 84 caacagccac acactacatc agtggctcaa agacaagaac aaaggagaaa tgtgagttgt 60 attattcttt cttcctatgt taatctaagt ttttgttaga tgagtctgtc ggtgtttgtg 120 120 <210> 85 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 85_PIK3CA <400> 85 agatatgatg cagccattga cctgtttaca cgttcatgtg ctggatactg tgtagctacc 60 ttcattttgg gaattggaga tcgtcacaat agtaacatca tggtgaaaga cgatggacaa 120 120 <210> 86 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 86_PIK3CA <400> 86 atatgatgca gccattgacc tgtttacacg ttcatgtgct ggatactgtg tagctacctt 60 cattttggga attggagatc gtcacaatag taacatcatg gtgaaagacg atggacaagt 120 120 <210> 87 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 87_PIK3CA <400> 87 attcaagaca ttttgtatct gcatatatca aactataaca taatttctta tttttgaaag 60 ctgtttcata tagattttgg acactttttg gatcacaaga agaaaaaatt tggttataaa 120 120 <210> 88 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 88_PIK3CA <400> 88 ctgtttcata tagattttgg acactttttg gatcacaaga agaaaaaatt tggttataaa 60 cgagaacgtg tgccatttgt tttgacacag gatttcttaa tagtgattag taaaggagcc 120 120 <210> 89 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 89_PIK3CA <400> 89 cgagaacgtg tgccatttgt tttgacacag gatttcttaa tagtgattag taaaggagcc 60 caagaatgca caaagacaag agaatttgag aggtgagctc gagcaattaa aaacacaaaa 120 120 <210> 90 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 90_PIK3CA <400> 90 caagaatgca caaagacaag agaatttgag aggtgagctc gagcaattaa aaacacaaaa 60 taaagagttc tggctgctct attagaaaca atcaatattt ttcaagcaat ttcaaaataa 120 120 <210> 91 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 91_PIK3CA <400> 91 gacctgaagg tattaacatc atttgctcca aactgaccaa actgttctta ttacttatag 60 gtttcaggag atgtgttaca aggcttatct agctattcga cagcatgcca atctcttcat 120 120 <210> 92 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 92_PIK3CA <400> 92 gtttcaggag atgtgttaca aggcttatct agctattcga cagcatgcca atctcttcat 60 aaatcttttc tcaatgatgc ttggctctgg aatgccagaa ctacaatctt ttgatgacat 120 120 <210> 93 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 93_PIK3CA <400> 93 aaatcttttc tcaatgatgc ttggctctgg aatgccagaa ctacaatctt ttgatgacat 60 tgcatacatt cgaaagaccc tagccttaga taaaactgag caagaggctt tggagtattt 120 120 <210> 94 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 94_PIK3CA <400> 94 tgcatacatt cgaaagaccc tagccttaga taaaactgag caagaggctt tggagtattt 60 catgaaacaa atgaatgatg cacatcatgg tggctggaca acaaaaatgg attggatctt 120 120 <210> 95 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 95_PIK3CA <400> 95 catgaaacaa atgaatgatg cacatcatgg tggctggaca acaaaaatgg attggatctt 60 ccacacaatt aaacagcatg cattgaactg aaaagataac tgagaaaatg aaagctcact 120 120 <210> 96 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 96_PIK3CA <400> 96 ccacacaatt aaacagcatg cattgaactg aaaagataac tgagaaaatg aaagctcact 60 ctggattcca cactgcactg ttaataactc tcagcaggca aagaccgatt gcataggaat 120 120 <210> 97 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 97_APC <400> 97 gttggctgtt ggtgaggaag gtgaagcact cagttgcctt ctcgggcctc ggcgccccct 60 atgtacgcct ccctgggctc gggtccggtc gcccctttgc ccgcttctgt accaccctca 120 120 <210> 98 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 98_APC <400> 98 atgtacgcct ccctgggctc gggtccggtc gcccctttgc ccgcttctgt accaccctca 60 gttctcgggt cctggagcac cggcggcagc aggagctgcg tccggcagga gacgaagagc 120 120 <210> 99 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 99_APC <400> 99 gttctcgggt cctggagcac cggcggcagc aggagctgcg tccggcagga gacgaagagc 60 ccgggcggcg ctcgtacttc tggccactgg gcgagcgtct ggcaggtgag tgaggctgca 120 120 <210> 100 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 100_APC <400> 100 ccgggcggcg ctcgtacttc tggccactgg gcgagcgtct ggcaggtgag tgaggctgca 60 ggcattgacg tctcctcccg gcaaagcttc ctcggctttg ccccgccgct gctcgggacc 120 120 <210> 101 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 101_APC <400> 101 cctggcgaca aggacacatg cattggtggc caaaagagag aggagacaaa accgctgcag 60 atggctgatg tgaatctagt ggaaagagct actggggatg agagaaagag gaggaggcag 120 120 <210> 102 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 102_APC <400> 102 gacacatgca ttggtggcca aaagagagag gagacaaaac cgctgcagat ggctgatgtg 60 aatctagtgg aaagagctac tggggatgag agaaagagga ggaggcaggt actgcagagc 120 120 <210> 103 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 103_APC <400> 103 aaaacaagca gccactaaat tttttagtag tgaatttcaa aatccttttt aaccttatag 60 gtccaagggt agccaaggat ggctgcagct tcatatgatc agttgttaaa gcaagttgag 120 120 <210> 104 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 104_APC <400> 104 gtccaagggt agccaaggat ggctgcagct tcatatgatc agttgttaaa gcaagttgag 60 gcactgaaga tggagaactc aaatcttcga caagagctag aagataattc caatcatctt 120 120 <210> 105 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 105_APC <400> 105 gcactgaaga tggagaactc aaatcttcga caagagctag aagataattc caatcatctt 60 acaaaactgg aaactgaggc atctaatatg aaggtatcaa gactgtgact tttaattgta 120 120 <210> 106 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 106_APC <400> 106 acaaaactgg aaactgaggc atctaatatg aaggtatcaa gactgtgact tttaattgta 60 gtttatccat ttttattcag tattccctct tgtaaacttg aggtaagaca ctttacttaa 120 120 <210> 107 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 107_APC <400> 107 aatttcatgt taatatattg tgttcttttt aacaggaagt acttaaacaa ctacaaggaa 60 gtattgaaga tgaagctatg gcttcttctg gacagattga tttattagag cgtcttaaag 120 120 <210> 108 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 108_APC <400> 108 gaagtactta aacaactaca aggaagtatt gaagatgaag ctatggcttc ttctggacag 60 attgatttat tagagcgtct taaaggtaga ttttaaaaag gtgttttaaa ataatttttt 120 120 <210> 109 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 109_APC <400> 109 agaatatttt agactgctta aagcaattgt tgtataaaaa cttgtttcta ttttatttag 60 agcttaactt agatagcagt aatttccctg gagtaaaact gcggtcaaaa atgtccctcc 120 120 <210> 110 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 110_APC <400> 110 agcttaactt agatagcagt aatttccctg gagtaaaact gcggtcaaaa atgtccctcc 60 gttcttatgg aagccgggaa ggatctgtat caagccgttc tggagagtgc agtcctgttc 120 120 <210> 111 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 111_APC <400> 111 gttcttatgg aagccgggaa ggatctgtat caagccgttc tggagagtgc agtcctgttc 60 ctatgggttc atttccaaga agagggtttg taaatggaag cagagaaagt actggatatt 120 120 <210> 112 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 112_APC <400> 112 ctatgggttc atttccaaga agagggtttg taaatggaag cagagaaagt actggatatt 60 tagaagaact tgagaaagag aggtaacttt tcttcatata gtaaacattg ccttgtgtac 120 120 <210> 113 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 113_APC <400> 113 tagaagaact tgagaaagag aggtaacttt tcttcatata gtaaacattg ccttgtgtac 60 tccagtttat tgttattttg taatataata tttaaattgt gaatttatag taggtgatag 120 120 <210> 114 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 114_APC <400> 114 aaaaaaaata ggtcattgct tcttgctgat cttgacaaag aagaaaagga aaaagactgg 60 tattacgctc aacttcagaa tctcactaaa agaatagata gtcttccttt aactgaaaat 120 120 <210> 115 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 115_APC <400> 115 gtcattgctt cttgctgatc ttgacaaaga agaaaaggaa aaagactggt attacgctca 60 acttcagaat ctcactaaaa gaatagatag tcttccttta actgaaaatg taagtaactt 120 120 <210> 116 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 116_APC <400> 116 ttttagtttt ccttacaaac agatatgacc agaaggcaat tggaatatga agcaaggcaa 60 atcagagttg cgatggaaga acaactaggt acctgccagg atatggaaaa acgagcacag 120 120 <210> 117 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 117_APC <400> 117 ttttccttac aaacagatat gaccagaagg caattggaat atgaagcaag gcaaatcaga 60 gttgcgatgg aagaacaact aggtacctgc caggatatgg aaaaacgagc acaggtaagt 120 120 <210> 118 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 118_APC <400> 118 aaaacataac taattaggtt tcttgtttta ttttagcgaa gaatagccag aattcagcaa 60 atcgaaaagg acatacttcg tatacgacag cttttacagt cccaagcaac agaagcagag 120 120 <210> 119 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 119_APC <400> 119 cgaagaatag ccagaattca gcaaatcgaa aaggacatac ttcgtatacg acagctttta 60 cagtcccaag caacagaagc agaggttagt aaattgcctt tcttgtttgt gggtataaaa 120 120 <210> 120 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 120_APC <400> 120 actccatctt aacagaggtc atctcagaac aagcatgaaa ccggctcaca tgatgctgag 60 cggcagaatg aaggtcaagg agtgggagaa atcaacatgg caacttctgg taatggtcag 120 120 <210> 121 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 121_APC <400> 121 aggtcatctc agaacaagca tgaaaccggc tcacatgatg ctgagcggca gaatgaaggt 60 caaggagtgg gagaaatcaa catggcaact tctggtaatg gtcaggtaaa taaattattt 120 120 <210> 122 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 122_APC <400> 122 tataatgtgc ttaattttta gggttcaact acacgaatgg accatgaaac agccagtgtt 60 ttgagttcta gtagcacaca ctctgcacct cgaaggctga caagtcatct gggaaccaag 120 120 <210> 123 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 123_APC <400> 123 ggttcaacta cacgaatgga ccatgaaaca gccagtgttt tgagttctag tagcacacac 60 tctgcacctc gaaggctgac aagtcatctg ggaaccaagg taacagaaga ttacaaaccc 120 120 <210> 124 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 124_APC <400> 124 ggtttttggc ttttggatat taaagtcgta attttgtttc taaactcatt tggcccacag 60 gtggaaatgg tgtattcatt gttgtcaatg cttggtactc atgataagga tgatatgtcg 120 120 <210> 125 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 125_APC <400> 125 gtggaaatgg tgtattcatt gttgtcaatg cttggtactc atgataagga tgatatgtcg 60 cgaactttgc tagctatgtc tagctcccaa gacagctgta tatccatgcg acagtctgga 120 120 <210> 126 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 126_APC <400> 126 cgaactttgc tagctatgtc tagctcccaa gacagctgta tatccatgcg acagtctgga 60 tgtcttcctc tcctcatcca gcttttacat ggcaatgaca aagactctgt attgttggga 120 120 <210> 127 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 127_APC <400> 127 tgtcttcctc tcctcatcca gcttttacat ggcaatgaca aagactctgt attgttggga 60 aattcccggg gcagtaaaga ggctcgggcc agggccagtg cagcactcca caacatcatt 120 120 <210> 128 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 128_APC <400> 128 aattcccggg gcagtaaaga ggctcgggcc agggccagtg cagcactcca caacatcatt 60 cactcacagc ctgatgacaa gagaggcagg cgtgaaatcc gagtccttca tcttttggaa 120 120 <210> 129 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 129_APC <400> 129 cactcacagc ctgatgacaa gagaggcagg cgtgaaatcc gagtccttca tcttttggaa 60 cagatacgcg cttactgtga aacctgttgg gagtggcagg aagctcatga accaggcatg 120 120 <210> 130 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 130_APC <400> 130 cagatacgcg cttactgtga aacctgttgg gagtggcagg aagctcatga accaggcatg 60 gaccaggaca aaaatccaag tatgttctct atagtgtaca tcgtagtgca tgtttcaaag 120 120 <210> 131 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 131_APC <400> 131 gaccaggaca aaaatccaag tatgttctct atagtgtaca tcgtagtgca tgtttcaaag 60 caaatgtgaa atttttaaac agaaaacatg tttagttaat atgctgtctt tatgactaag 120 120 <210> 132 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 132_APC <400> 132 gtttatgttg attttatttt tcagtgccag ctcctgttga acatcagatc tgtcctgctg 60 tgtgtgttct aatgaaactt tcatttgatg aagagcatag acatgcaatg aatgaactag 120 120 <210> 133 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 133_APC <400> 133 tgccagctcc tgttgaacat cagatctgtc ctgctgtgtg tgttctaatg aaactttcat 60 ttgatgaaga gcatagacat gcaatgaatg aactaggtaa gacaaaaatg ttttttaatg 120 120 <210> 134 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 134_APC <400> 134 aaaataaaac ctagactcag tatttgttcc tcttccttct tcaggtagga aggctacccg 60 gggcatttca tcacaggagc tagggcaggg gctttcaggt gaggagcagg atggggcctc 120 120 <210> 135 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 135_APC <400> 135 tttgttcctc ttccttcttc aggtaggaag gctacccggg gcatttcatc acaggagcta 60 gggcaggggc tttcaggtga ggagcaggat ggggcctctg ggggtgtgac tgctggggac 120 120 <210> 136 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 136_APC <400> 136 tggtaccagt ttgttttatt ttagatgatt gtctttttcc tcttgccctt tttaaattag 60 ggggactaca ggccattgca gaattattgc aagtggactg tgaaatgtat gggcttacta 120 120 <210> 137 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 137_APC <400> 137 ggggactaca ggccattgca gaattattgc aagtggactg tgaaatgtat gggcttacta 60 atgaccacta cagtattaca ctaagacgat atgctggaat ggctttgaca aacttgactt 120 120 <210> 138 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 138_APC <400> 138 atgaccacta cagtattaca ctaagacgat atgctggaat ggctttgaca aacttgactt 60 ttggagatgt agccaacaag gtatgttttt ataacatgta tttcttaaga tagctcaggt 120 120 <210> 139 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 139_APC <400> 139 ttggagatgt agccaacaag gtatgttttt ataacatgta tttcttaaga tagctcaggt 60 atgagttaat ttactttcat acaaatacat tttactgatt ttcttttttt tcactctcct 120 120 <210> 140 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 140_APC <400> 140 gttgtctttt taatgatcct ctattctgta tttaatttac aggctacgct atgctctatg 60 aaaggctgca tgagagcact tgtggcccaa ctaaaatctg aaagtgaaga cttacagcag 120 120 <210> 141 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 141_APC <400> 141 gctacgctat gctctatgaa aggctgcatg agagcacttg tggcccaact aaaatctgaa 60 agtgaagact tacagcaggt actatttaga atttcacctg tttttctttt ttctcttttt 120 120 <210> 142 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 142_APC <400> 142 caggttattg cgagtgtttt gaggaatttg tcttggcgag cagatgtaaa tagtaaaaag 60 acgttgcgag aagttggaag tgtgaaagca ttgatggaat gtgctttaga agttaaaaag 120 120 <210> 143 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 143_APC <400> 143 gttattgcga gtgttttgag gaatttgtct tggcgagcag atgtaaatag taaaaagacg 60 ttgcgagaag ttggaagtgt gaaagcattg atggaatgtg ctttagaagt taaaaaggta 120 120 <210> 144 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 144_APC <400> 144 aagttaatga gagacaaatt ccaactctaa ttagatgacc catattctgt ttcttactag 60 gaatcaaccc tcaaaagcgt attgagtgcc ttatggaatt tgtcagcaca ttgcactgag 120 120 <210> 145 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 145_APC <400> 145 gaatcaaccc tcaaaagcgt attgagtgcc ttatggaatt tgtcagcaca ttgcactgag 60 aataaagctg atatatgtgc tgtagatggt gcacttgcat ttttggttgg cactcttact 120 120 <210> 146 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 146_APC <400> 146 aataaagctg atatatgtgc tgtagatggt gcacttgcat ttttggttgg cactcttact 60 taccggagcc agacaaacac tttagccatt attgaaagtg gaggtgggat attacggaat 120 120 <210> 147 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 147_APC <400> 147 taccggagcc agacaaacac tttagccatt attgaaagtg gaggtgggat attacggaat 60 gtgtccagct tgatagctac aaatgaggac cacaggtata tatagagttt tatattactt 120 120 <210> 148 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 148_APC <400> 148 gtgtccagct tgatagctac aaatgaggac cacaggtata tatagagttt tatattactt 60 ttaaagtaca gaattcatac tctcaaaaag acctaattgt aagcaatgtt ttatataatc 120 120 <210> 149 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 149_APC <400> 149 tttgttgtta ctgcatacac attgtgacct taattttgtg atctcttgat tttatttcag 60 gcaaatccta agagagaaca actgtctaca aactttatta caacacttaa aatctcatag 120 120 <210> 150 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 150_APC <400> 150 gcaaatccta agagagaaca actgtctaca aactttatta caacacttaa aatctcatag 60 tttgacaata gtcagtaatg catgtggaac tttgtggaat ctctcagcaa gaaatcctaa 120 120 <210> 151 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 151_APC <400> 151 tttgacaata gtcagtaatg catgtggaac tttgtggaat ctctcagcaa gaaatcctaa 60 agaccaggaa gcattatggg acatgggggc agttagcatg ctcaagaacc tcattcattc 120 120 <210> 152 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 152_APC <400> 152 agaccaggaa gcattatggg acatgggggc agttagcatg ctcaagaacc tcattcattc 60 aaagcacaaa atgattgcta tgggaagtgc tgcagcttta aggaatctca tggcaaatag 120 120 <210> 153 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 153_APC <400> 153 aaagcacaaa atgattgcta tgggaagtgc tgcagcttta aggaatctca tggcaaatag 60 gcctgcgaag tacaaggatg ccaatattat gtctcctggc tcaagcttgc catctcttca 120 120 <210> 154 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 154_APC <400> 154 gcctgcgaag tacaaggatg ccaatattat gtctcctggc tcaagcttgc catctcttca 60 tgttaggaaa caaaaagccc tagaagcaga attagatgct cagcacttat cagaaacttt 120 120 <210> 155 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 155_APC <400> 155 tgttaggaaa caaaaagccc tagaagcaga attagatgct cagcacttat cagaaacttt 60 tgacaatata gacaatttaa gtcccaaggc atctcatcgt agtaagcaga gacacaagca 120 120 <210> 156 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 156_APC <400> 156 tgacaatata gacaatttaa gtcccaaggc atctcatcgt agtaagcaga gacacaagca 60 aagtctctat ggtgattatg tttttgacac caatcgacat gatgataata ggtcagacaa 120 120 <210> 157 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 157_APC <400> 157 aagtctctat ggtgattatg tttttgacac caatcgacat gatgataata ggtcagacaa 60 ttttaatact ggcaacatga ctgtcctttc accatatttg aatactacag tgttacccag 120 120 <210> 158 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 158_APC <400> 158 ttttaatact ggcaacatga ctgtcctttc accatatttg aatactacag tgttacccag 60 ctcctcttca tcaagaggaa gcttagatag ttctcgttct gaaaaagata gaagtttgga 120 120 <210> 159 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 159_APC <400> 159 ctcctcttca tcaagaggaa gcttagatag ttctcgttct gaaaaagata gaagtttgga 60 gagagaacgc ggaattggtc taggcaacta ccatccagca acagaaaatc caggaacttc 120 120 <210> 160 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 160_APC <400> 160 gagagaacgc ggaattggtc taggcaacta ccatccagca acagaaaatc caggaacttc 60 ttcaaagcga ggtttgcaga tctccaccac tgcagcccag attgccaaag tcatggaaga 120 120 <210> 161 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 161_APC <400> 161 ttcaaagcga ggtttgcaga tctccaccac tgcagcccag attgccaaag tcatggaaga 60 agtgtcagcc attcatacct ctcaggaaga cagaagttct gggtctacca ctgaattaca 120 120 <210> 162 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 162_APC <400> 162 agtgtcagcc attcatacct ctcaggaaga cagaagttct gggtctacca ctgaattaca 60 ttgtgtgaca gatgagagaa atgcacttag aagaagctct gctgcccata cacattcaaa 120 120 <210> 163 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 163_APC <400> 163 ttgtgtgaca gatgagagaa atgcacttag aagaagctct gctgcccata cacattcaaa 60 cacttacaat ttcactaagt cggaaaattc aaataggaca tgttctatgc cttatgccaa 120 120 <210> 164 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 164_APC <400> 164 cacttacaat ttcactaagt cggaaaattc aaataggaca tgttctatgc cttatgccaa 60 attagaatac aagagatctt caaatgatag tttaaatagt gtcagtagta gtgatggtta 120 120 <210> 165 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 165_APC <400> 165 attagaatac aagagatctt caaatgatag tttaaatagt gtcagtagta gtgatggtta 60 tggtaaaaga ggtcaaatga aaccctcgat tgaatcctat tctgaagatg atgaaagtaa 120 120 <210> 166 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 166_APC <400> 166 tggtaaaaga ggtcaaatga aaccctcgat tgaatcctat tctgaagatg atgaaagtaa 60 gttttgcagt tatggtcaat acccagccga cctagcccat aaaatacata gtgcaaatca 120 120 <210> 167 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 167_APC <400> 167 gttttgcagt tatggtcaat acccagccga cctagcccat aaaatacata gtgcaaatca 60 tatggatgat aatgatggag aactagatac accaataaat tatagtctta aatattcaga 120 120 <210> 168 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 168_APC <400> 168 tatggatgat aatgatggag aactagatac accaataaat tatagtctta aatattcaga 60 tgagcagttg aactctggaa ggcaaagtcc ttcacagaat gaaagatggg caagacccaa 120 120 <210> 169 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 169_APC <400> 169 tgagcagttg aactctggaa ggcaaagtcc ttcacagaat gaaagatggg caagacccaa 60 acacataata gaagatgaaa taaaacaaag tgagcaaaga caatcaagga atcaaagtac 120 120 <210> 170 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 170_APC <400> 170 acacataata gaagatgaaa taaaacaaag tgagcaaaga caatcaagga atcaaagtac 60 aacttatcct gtttatactg agagcactga tgataaacac ctcaagttcc aaccacattt 120 120 <210> 171 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 171_APC <400> 171 aacttatcct gtttatactg agagcactga tgataaacac ctcaagttcc aaccacattt 60 tggacagcag gaatgtgttt ctccatacag gtcacgggga gccaatggtt cagaaacaaa 120 120 <210> 172 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 172_APC <400> 172 tggacagcag gaatgtgttt ctccatacag gtcacgggga gccaatggtt cagaaacaaa 60 tcgagtgggt tctaatcatg gaattaatca aaatgtaagc cagtctttgt gtcaagaaga 120 120 <210> 173 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 173_APC <400> 173 tcgagtgggt tctaatcatg gaattaatca aaatgtaagc cagtctttgt gtcaagaaga 60 tgactatgaa gatgataagc ctaccaatta tagtgaacgt tactctgaag aagaacagca 120 120 <210> 174 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 174_APC <400> 174 tgactatgaa gatgataagc ctaccaatta tagtgaacgt tactctgaag aagaacagca 60 tgaagaagaa gagagaccaa caaattatag cataaaatat aatgaagaga aacgtcatgt 120 120 <210> 175 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 175_APC <400> 175 tgaagaagaa gagagaccaa caaattatag cataaaatat aatgaagaga aacgtcatgt 60 ggatcagcct attgattata gtttaaaata tgccacagat attccttcat cacagaaaca 120 120 <210> 176 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 176_APC <400> 176 ggatcagcct attgattata gtttaaaata tgccacagat attccttcat cacagaaaca 60 gtcattttca ttctcaaaga gttcatctgg acaaagcagt aaaaccgaac atatgtcttc 120 120 <210> 177 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 177_APC <400> 177 gtcattttca ttctcaaaga gttcatctgg acaaagcagt aaaaccgaac atatgtcttc 60 aagcagtgag aatacgtcca caccttcatc taatgccaag aggcagaatc agctccatcc 120 120 <210> 178 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 178_APC <400> 178 aagcagtgag aatacgtcca caccttcatc taatgccaag aggcagaatc agctccatcc 60 aagttctgca cagagtagaa gtggtcagcc tcaaaaggct gccacttgca aagtttcttc 120 120 <210> 179 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 179_APC <400> 179 aagttctgca cagagtagaa gtggtcagcc tcaaaaggct gccacttgca aagtttcttc 60 tattaaccaa gaaacaatac agacttattg tgtagaagat actccaatat gtttttcaag 120 120 <210> 180 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 180_APC <400> 180 tattaaccaa gaaacaatac agacttattg tgtagaagat actccaatat gtttttcaag 60 atgtagttca ttatcatctt tgtcatcagc tgaagatgaa ataggatgta atcagacgac 120 120 <210> 181 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 181_APC <400> 181 atgtagttca ttatcatctt tgtcatcagc tgaagatgaa ataggatgta atcagacgac 60 acaggaagca gattctgcta ataccctgca aatagcagaa ataaaagaaa agattggaac 120 120 <210> 182 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 182_APC <400> 182 acaggaagca gattctgcta ataccctgca aatagcagaa ataaaagaaa agattggaac 60 taggtcagct gaagatcctg tgagcgaagt tccagcagtg tcacagcacc ctagaaccaa 120 120 <210> 183 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 183_APC <400> 183 taggtcagct gaagatcctg tgagcgaagt tccagcagtg tcacagcacc ctagaaccaa 60 atccagcaga ctgcagggtt ctagtttatc ttcagaatca gccaggcaca aagctgttga 120 120 <210> 184 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 184_APC <400> 184 atccagcaga ctgcagggtt ctagtttatc ttcagaatca gccaggcaca aagctgttga 60 attttcttca ggagcgaaat ctccctccaa aagtggtgct cagacaccca aaagtccacc 120 120 <210> 185 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 185_APC <400> 185 attttcttca ggagcgaaat ctccctccaa aagtggtgct cagacaccca aaagtccacc 60 tgaacactat gttcaggaga ccccactcat gtttagcaga tgtacttctg tcagttcact 120 120 <210> 186 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 186_APC <400> 186 tgaacactat gttcaggaga ccccactcat gtttagcaga tgtacttctg tcagttcact 60 tgatagtttt gagagtcgtt cgattgccag ctccgttcag agtgaaccat gcagtggaat 120 120 <210> 187 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 187_APC <400> 187 tgatagtttt gagagtcgtt cgattgccag ctccgttcag agtgaaccat gcagtggaat 60 ggtaagtggc attataagcc ccagtgatct tccagatagc cctggacaaa ccatgccacc 120 120 <210> 188 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 188_APC <400> 188 ggtaagtggc attataagcc ccagtgatct tccagatagc cctggacaaa ccatgccacc 60 aagcagaagt aaaacacctc caccacctcc tcaaacagct caaaccaagc gagaagtacc 120 120 <210> 189 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 189_APC <400> 189 aagcagaagt aaaacacctc caccacctcc tcaaacagct caaaccaagc gagaagtacc 60 taaaaataaa gcacctactg ctgaaaagag agagagtgga cctaagcaag ctgcagtaaa 120 120 <210> 190 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 190_APC <400> 190 taaaaataaa gcacctactg ctgaaaagag agagagtgga cctaagcaag ctgcagtaaa 60 tgctgcagtt cagagggtcc aggttcttcc agatgctgat actttattac attttgccac 120 120 <210> 191 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 191_APC <400> 191 tgctgcagtt cagagggtcc aggttcttcc agatgctgat actttattac attttgccac 60 ggaaagtact ccagatggat tttcttgttc atccagcctg agtgctctga gcctcgatga 120 120 <210> 192 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 192_APC <400> 192 ggaaagtact ccagatggat tttcttgttc atccagcctg agtgctctga gcctcgatga 60 gccatttata cagaaagatg tggaattaag aataatgcct ccagttcagg aaaatgacaa 120 120 <210> 193 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 193_APC <400> 193 gccatttata cagaaagatg tggaattaag aataatgcct ccagttcagg aaaatgacaa 60 tgggaatgaa acagaatcag agcagcctaa agaatcaaat gaaaaccaag agaaagaggc 120 120 <210> 194 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 194_APC <400> 194 tgggaatgaa acagaatcag agcagcctaa agaatcaaat gaaaaccaag agaaagaggc 60 agaaaaaact attgattctg aaaaggacct attagatgat tcagatgatg atgatattga 120 120 <210> 195 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 195_APC <400> 195 agaaaaaact attgattctg aaaaggacct attagatgat tcagatgatg atgatattga 60 aatactagaa gaatgtatta tttctgccat gccaacaaag tcatcacgta aagcaaaaaa 120 120 <210> 196 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 196_APC <400> 196 aatactagaa gaatgtatta tttctgccat gccaacaaag tcatcacgta aagcaaaaaa 60 gccagcccag actgcttcaa aattacctcc acctgtggca aggaaaccaa gtcagctgcc 120 120 <210> 197 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 197_APC <400> 197 gccagcccag actgcttcaa aattacctcc acctgtggca aggaaaccaa gtcagctgcc 60 tgtgtacaaa cttctaccat cacaaaacag gttgcaaccc caaaagcatg ttagttttac 120 120 <210> 198 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 198_APC <400> 198 tgtgtacaaa cttctaccat cacaaaacag gttgcaaccc caaaagcatg ttagttttac 60 accgggggat gatatgccac gggtgtattg tgttgaaggg acacctataa acttttccac 120 120 <210> 199 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 199_APC <400> 199 accgggggat gatatgccac gggtgtattg tgttgaaggg acacctataa acttttccac 60 agctacatct ctaagtgatc taacaatcga atcccctcca aatgagttag ctgctggaga 120 120 <210> 200 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 200_APC <400> 200 agctacatct ctaagtgatc taacaatcga atcccctcca aatgagttag ctgctggaga 60 aggagttaga ggaggggcac agtcaggtga atttgaaaaa cgagatacca ttcctacaga 120 120 <210> 201 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 201_APC <400> 201 aggagttaga ggaggggcac agtcaggtga atttgaaaaa cgagatacca ttcctacaga 60 aggcagaagt acagatgagg ctcaaggagg aaaaacctca tctgtaacca tacctgaatt 120 120 <210> 202 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 202_APC <400> 202 aggcagaagt acagatgagg ctcaaggagg aaaaacctca tctgtaacca tacctgaatt 60 ggatgacaat aaagcagagg aaggtgatat tcttgcagaa tgcattaatt ctgctatgcc 120 120 <210> 203 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 203_APC <400> 203 ggatgacaat aaagcagagg aaggtgatat tcttgcagaa tgcattaatt ctgctatgcc 60 caaagggaaa agtcacaagc ctttccgtgt gaaaaagata atggaccagg tccagcaagc 120 120 <210> 204 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 204_APC <400> 204 caaagggaaa agtcacaagc ctttccgtgt gaaaaagata atggaccagg tccagcaagc 60 atctgcgtct tcttctgcac ccaacaaaaa tcagttagat ggtaagaaaa agaaaccaac 120 120 <210> 205 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 205_APC <400> 205 atctgcgtct tcttctgcac ccaacaaaaa tcagttagat ggtaagaaaa agaaaccaac 60 ttcaccagta aaacctatac cacaaaatac tgaatatagg acacgtgtaa gaaaaaatgc 120 120 <210> 206 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 206_APC <400> 206 ttcaccagta aaacctatac cacaaaatac tgaatatagg acacgtgtaa gaaaaaatgc 60 agactcaaaa aataatttaa atgctgagag agttttctca gacaacaaag attcaaagaa 120 120 <210> 207 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 207_APC <400> 207 agactcaaaa aataatttaa atgctgagag agttttctca gacaacaaag attcaaagaa 60 acagaatttg aaaaataatt ccaaggtctt caatgataag ctcccaaata atgaagatag 120 120 <210> 208 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 208_APC <400> 208 acagaatttg aaaaataatt ccaaggtctt caatgataag ctcccaaata atgaagatag 60 agtcagagga agttttgctt ttgattcacc tcatcattac acgcctattg aaggaactcc 120 120 <210> 209 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 209_APC <400> 209 agtcagagga agttttgctt ttgattcacc tcatcattac acgcctattg aaggaactcc 60 ttactgtttt tcacgaaatg attctttgag ttctctagat tttgatgatg atgatgttga 120 120 <210> 210 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 210_APC <400> 210 ttactgtttt tcacgaaatg attctttgag ttctctagat tttgatgatg atgatgttga 60 cctttccagg gaaaaggctg aattaagaaa ggcaaaagaa aataaggaat cagaggctaa 120 120 <210> 211 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 211_APC <400> 211 cctttccagg gaaaaggctg aattaagaaa ggcaaaagaa aataaggaat cagaggctaa 60 agttaccagc cacacagaac taacctccaa ccaacaatca gctaataaga cacaagctat 120 120 <210> 212 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 212_APC <400> 212 agttaccagc cacacagaac taacctccaa ccaacaatca gctaataaga cacaagctat 60 tgcaaagcag ccaataaatc gaggtcagcc taaacccata cttcagaaac aatccacttt 120 120 <210> 213 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 213_APC <400> 213 tgcaaagcag ccaataaatc gaggtcagcc taaacccata cttcagaaac aatccacttt 60 tccccagtca tccaaagaca taccagacag aggggcagca actgatgaaa agttacagaa 120 120 <210> 214 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 214_APC <400> 214 tccccagtca tccaaagaca taccagacag aggggcagca actgatgaaa agttacagaa 60 ttttgctatt gaaaatactc cggtttgctt ttctcataat tcctctctga gttctctcag 120 120 <210> 215 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 215_APC <400> 215 ttttgctatt gaaaatactc cggtttgctt ttctcataat tcctctctga gttctctcag 60 tgacattgac caagaaaaca acaataaaga aaatgaacct atcaaagaga ctgagccccc 120 120 <210> 216 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 216_APC <400> 216 tgacattgac caagaaaaca acaataaaga aaatgaacct atcaaagaga ctgagccccc 60 tgactcacag ggagaaccaa gtaaacctca agcatcaggc tatgctccta aatcatttca 120 120 <210> 217 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 217_APC <400> 217 tgactcacag ggagaaccaa gtaaacctca agcatcaggc tatgctccta aatcatttca 60 tgttgaagat accccagttt gtttctcaag aaacagttct ctcagttctc ttagtattga 120 120 <210> 218 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 218_APC <400> 218 tgttgaagat accccagttt gtttctcaag aaacagttct ctcagttctc ttagtattga 60 ctctgaagat gacctgttgc aggaatgtat aagctccgca atgccaaaaa agaaaaagcc 120 120 <210> 219 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 219_APC <400> 219 ctctgaagat gacctgttgc aggaatgtat aagctccgca atgccaaaaa agaaaaagcc 60 ttcaagactc aagggtgata atgaaaaaca tagtcccaga aatatgggtg gcatattagg 120 120 <210> 220 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 220_APC <400> 220 ttcaagactc aagggtgata atgaaaaaca tagtcccaga aatatgggtg gcatattagg 60 tgaagatctg acacttgatt tgaaagatat acagagacca gattcagaac atggtctatc 120 120 <210> 221 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 221_APC <400> 221 tgaagatctg acacttgatt tgaaagatat acagagacca gattcagaac atggtctatc 60 ccctgattca gaaaattttg attggaaagc tattcaggaa ggtgcaaatt ccatagtaag 120 120 <210> 222 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 222_APC <400> 222 ccctgattca gaaaattttg attggaaagc tattcaggaa ggtgcaaatt ccatagtaag 60 tagtttacat caagctgctg ctgctgcatg tttatctaga caagcttcgt ctgattcaga 120 120 <210> 223 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 223_APC <400> 223 tagtttacat caagctgctg ctgctgcatg tttatctaga caagcttcgt ctgattcaga 60 ttccatcctt tccctgaaat caggaatctc tctgggatca ccatttcatc ttacacctga 120 120 <210> 224 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 224_APC <400> 224 ttccatcctt tccctgaaat caggaatctc tctgggatca ccatttcatc ttacacctga 60 tcaagaagaa aaacccttta caagtaataa aggcccacga attctaaaac caggggagaa 120 120 <210> 225 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 225_APC <400> 225 tcaagaagaa aaacccttta caagtaataa aggcccacga attctaaaac caggggagaa 60 aagtacattg gaaactaaaa agatagaatc tgaaagtaaa ggaatcaaag gaggaaaaaa 120 120 <210> 226 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 226_APC <400> 226 aagtacattg gaaactaaaa agatagaatc tgaaagtaaa ggaatcaaag gaggaaaaaa 60 agtttataaa agtttgatta ctggaaaagt tcgatctaat tcagaaattt caggccaaat 120 120 <210> 227 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 227_APC <400> 227 agtttataaa agtttgatta ctggaaaagt tcgatctaat tcagaaattt caggccaaat 60 gaaacagccc cttcaagcaa acatgccttc aatctctcga ggcaggacaa tgattcatat 120 120 <210> 228 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 228_APC <400> 228 gaaacagccc cttcaagcaa acatgccttc aatctctcga ggcaggacaa tgattcatat 60 tccaggagtt cgaaatagct cctcaagtac aagtcctgtt tctaaaaaag gcccacccct 120 120 <210> 229 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 229_APC <400> 229 tccaggagtt cgaaatagct cctcaagtac aagtcctgtt tctaaaaaag gcccacccct 60 taagactcca gcctccaaaa gccctagtga aggtcaaaca gccaccactt ctcctagagg 120 120 <210> 230 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 230_APC <400> 230 taagactcca gcctccaaaa gccctagtga aggtcaaaca gccaccactt ctcctagagg 60 agccaagcca tctgtgaaat cagaattaag ccctgttgcc aggcagacat cccaaatagg 120 120 <210> 231 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 231_APC <400> 231 agccaagcca tctgtgaaat cagaattaag ccctgttgcc aggcagacat cccaaatagg 60 tgggtcaagt aaagcacctt ctagatcagg atctagagat tcgacccctt caagacctgc 120 120 <210> 232 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 232_APC <400> 232 tgggtcaagt aaagcacctt ctagatcagg atctagagat tcgacccctt caagacctgc 60 ccagcaacca ttaagtagac ctatacagtc tcctggccga aactcaattt cccctggtag 120 120 <210> 233 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 233_APC <400> 233 ccagcaacca ttaagtagac ctatacagtc tcctggccga aactcaattt cccctggtag 60 aaatggaata agtcctccta acaaattatc tcaacttcca aggacatcat cccctagtac 120 120 <210> 234 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 234_APC <400> 234 aaatggaata agtcctccta acaaattatc tcaacttcca aggacatcat cccctagtac 60 tgcttcaact aagtcctcag gttctggaaa aatgtcatat acatctccag gtagacagat 120 120 <210> 235 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 235_APC <400> 235 tgcttcaact aagtcctcag gttctggaaa aatgtcatat acatctccag gtagacagat 60 gagccaacag aaccttacca aacaaacagg tttatccaag aatgccagta gtattccaag 120 120 <210> 236 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 236_APC <400> 236 gagccaacag aaccttacca aacaaacagg tttatccaag aatgccagta gtattccaag 60 aagtgagtct gcctccaaag gactaaatca gatgaataat ggtaatggag ccaataaaaa 120 120 <210> 237 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 237_APC <400> 237 aagtgagtct gcctccaaag gactaaatca gatgaataat ggtaatggag ccaataaaaa 60 ggtagaactt tctagaatgt cttcaactaa atcaagtgga agtgaatctg atagatcaga 120 120 <210> 238 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 238_APC <400> 238 ggtagaactt tctagaatgt cttcaactaa atcaagtgga agtgaatctg atagatcaga 60 aagacctgta ttagtacgcc agtcaacttt catcaaagaa gctccaagcc caaccttaag 120 120 <210> 239 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 239_APC <400> 239 aagacctgta ttagtacgcc agtcaacttt catcaaagaa gctccaagcc caaccttaag 60 aagaaaattg gaggaatctg cttcatttga atctctttct ccatcatcta gaccagcttc 120 120 <210> 240 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 240_APC <400> 240 aagaaaattg gaggaatctg cttcatttga atctctttct ccatcatcta gaccagcttc 60 tcccactagg tcccaggcac aaactccagt tttaagtcct tcccttcctg atatgtctct 120 120 <210> 241 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 241_APC <400> 241 tcccactagg tcccaggcac aaactccagt tttaagtcct tcccttcctg atatgtctct 60 atccacacat tcgtctgttc aggctggtgg atggcgaaaa ctcccaccta atctcagtcc 120 120 <210> 242 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 242_APC <400> 242 atccacacat tcgtctgttc aggctggtgg atggcgaaaa ctcccaccta atctcagtcc 60 cactatagag tataatgatg gaagaccagc aaagcgccat gatattgcac ggtctcattc 120 120 <210> 243 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 243_APC <400> 243 cactatagag tataatgatg gaagaccagc aaagcgccat gatattgcac ggtctcattc 60 tgaaagtcct tctagacttc caatcaatag gtcaggaacc tggaaacgtg agcacagcaa 120 120 <210> 244 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 244_APC <400> 244 tgaaagtcct tctagacttc caatcaatag gtcaggaacc tggaaacgtg agcacagcaa 60 acattcatca tcccttcctc gagtaagcac ttggagaaga actggaagtt catcttcaat 120 120 <210> 245 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 245_APC <400> 245 acattcatca tcccttcctc gagtaagcac ttggagaaga actggaagtt catcttcaat 60 tctttctgct tcatcagaat ccagtgaaaa agcaaaaagt gaggatgaaa aacatgtgaa 120 120 <210> 246 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 246_APC <400> 246 tctttctgct tcatcagaat ccagtgaaaa agcaaaaagt gaggatgaaa aacatgtgaa 60 ctctatttca ggaaccaaac aaagtaaaga aaaccaagta tccgcaaaag gaacatggag 120 120 <210> 247 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 247_APC <400> 247 ctctatttca ggaaccaaac aaagtaaaga aaaccaagta tccgcaaaag gaacatggag 60 aaaaataaaa gaaaatgaat tttctcccac aaatagtact tctcagaccg tttcctcagg 120 120 <210> 248 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 248_APC <400> 248 aaaaataaaa gaaaatgaat tttctcccac aaatagtact tctcagaccg tttcctcagg 60 tgctacaaat ggtgctgaat caaagactct aatttatcaa atggcacctg ctgtttctaa 120 120 <210> 249 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 249_APC <400> 249 tgctacaaat ggtgctgaat caaagactct aatttatcaa atggcacctg ctgtttctaa 60 aacagaggat gtttgggtga gaattgagga ctgtcccatt aacaatccta gatctggaag 120 120 <210> 250 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 250_APC <400> 250 aacagaggat gtttgggtga gaattgagga ctgtcccatt aacaatccta gatctggaag 60 atctcccaca ggtaatactc ccccggtgat tgacagtgtt tcagaaaagg caaatccaaa 120 120 <210> 251 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 251_APC <400> 251 atctcccaca ggtaatactc ccccggtgat tgacagtgtt tcagaaaagg caaatccaaa 60 cattaaagat tcaaaagata atcaggcaaa acaaaatgtg ggtaatggca gtgttcccat 120 120 <210> 252 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 252_APC <400> 252 cattaaagat tcaaaagata atcaggcaaa acaaaatgtg ggtaatggca gtgttcccat 60 gcgtaccgtg ggtttggaaa atcgcctgaa ctcctttatt caggtggatg cccctgacca 120 120 <210> 253 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 253_APC <400> 253 gcgtaccgtg ggtttggaaa atcgcctgaa ctcctttatt caggtggatg cccctgacca 60 aaaaggaact gagataaaac caggacaaaa taatcctgtc cctgtatcag agactaatga 120 120 <210> 254 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 254_APC <400> 254 aaaaggaact gagataaaac caggacaaaa taatcctgtc cctgtatcag agactaatga 60 aagttctata gtggaacgta ccccattcag ttctagcagc tcaagcaaac acagttcacc 120 120 <210> 255 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 255_APC <400> 255 aagttctata gtggaacgta ccccattcag ttctagcagc tcaagcaaac acagttcacc 60 tagtgggact gttgctgcca gagtgactcc ttttaattac aacccaagcc ctaggaaaag 120 120 <210> 256 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 256_APC <400> 256 tagtgggact gttgctgcca gagtgactcc ttttaattac aacccaagcc ctaggaaaag 60 cagcgcagat agcacttcag ctcggccatc tcagatccca actccagtga ataacaacac 120 120 <210> 257 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 257_APC <400> 257 cagcgcagat agcacttcag ctcggccatc tcagatccca actccagtga ataacaacac 60 aaagaagcga gattccaaaa ctgacagcac agaatccagt ggaacccaaa gtcctaagcg 120 120 <210> 258 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 258_APC <400> 258 aaagaagcga gattccaaaa ctgacagcac agaatccagt ggaacccaaa gtcctaagcg 60 ccattctggg tcttaccttg tgacatctgt ttaaaagaga ggaagaatga aactaagaaa 120 120 <210> 259 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 259_APC <400> 259 ccattctggg tcttaccttg tgacatctgt ttaaaagaga ggaagaatga aactaagaaa 60 attctatgtt aattacaact gctatataga cattttgttt caaatgaaac tttaaaagac 120 120 <210> 260 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 260_EGFR <400> 260 gagagccgga gcgagctctt cggggagcag cgatgcgacc ctccgggacg gccggggcag 60 cgctcctggc gctgctggct gcgctctgcc cggcgagtcg ggctctggag gaaaagaaag 120 120 <210> 261 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 261_EGFR <400> 261 atgcgaccct ccgggacggc cggggcagcg ctcctggcgc tgctggctgc gctctgcccg 60 gcgagtcggg ctctggagga aaagaaaggt aagggcgtgt ctcgccggct cccgcgccgc 120 120 <210> 262 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 262_EGFR <400> 262 tttattttag tttttctgca tttctcagta tttcatgtga tatctgtctt tttcttccag 60 tttgccaagg cacgagtaac aagctcacgc agttgggcac ttttgaagat cattttctca 120 120 <210> 263 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 263_EGFR <400> 263 tttgccaagg cacgagtaac aagctcacgc agttgggcac ttttgaagat cattttctca 60 gcctccagag gatgttcaat aactgtgagg tggtccttgg gaatttggaa attacctatg 120 120 <210> 264 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 264_EGFR <400> 264 gcctccagag gatgttcaat aactgtgagg tggtccttgg gaatttggaa attacctatg 60 tgcagaggaa ttatgatctt tccttcttaa aggttggtga ctttgatttt cctacacaaa 120 120 <210> 265 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 265_EGFR <400> 265 tgcagaggaa ttatgatctt tccttcttaa aggttggtga ctttgatttt cctacacaaa 60 taaaattgga gaaaatctaa gtggagaaag gcctgggcag aattccactt gaagtgtgtt 120 120 <210> 266 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 266_EGFR <400> 266 gaccttgagt tcttgagttc ctcaaaagag aaatcacgca tttatgtttt ctcttcttag 60 accatccagg aggtggctgg ttatgtcctc attgccctca acacagtgga gcgaattcct 120 120 <210> 267 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 267_EGFR <400> 267 accatccagg aggtggctgg ttatgtcctc attgccctca acacagtgga gcgaattcct 60 ttggaaaacc tgcagatcat cagaggaaat atgtactacg aaaattccta tgccttagca 120 120 <210> 268 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 268_EGFR <400> 268 ttggaaaacc tgcagatcat cagaggaaat atgtactacg aaaattccta tgccttagca 60 gtcttatcta actatgatgc aaataaaacc ggactgaagg agctgcccat gagaaattta 120 120 <210> 269 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 269_EGFR <400> 269 gtcttatcta actatgatgc aaataaaacc ggactgaagg agctgcccat gagaaattta 60 cagggtgaga ggctgggatg ccaaggctgg gggttcataa atgcagacag cagttccgat 120 120 <210> 270 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 270_EGFR <400> 270 cagggtgaga ggctgggatg ccaaggctgg gggttcataa atgcagacag cagttccgat 60 ggctcccagc gagcttgtca ctcaattcca cctcggagaa ggcttttatt tttacccagt 120 120 <210> 271 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 271_EGFR <400> 271 ccttcatggg aatttaaagg agctggaaag agtgctcacc gcagttccat tctcccgcag 60 aaatcctgca tggcgccgtg cggttcagca acaaccctgc cctgtgcaac gtggagagca 120 120 <210> 272 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 272_EGFR <400> 272 aaatcctgca tggcgccgtg cggttcagca acaaccctgc cctgtgcaac gtggagagca 60 tccagtggcg ggacatagtc agcagtgact ttctcagcaa catgtcgatg gacttccaga 120 120 <210> 273 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 273_EGFR <400> 273 tccagtggcg ggacatagtc agcagtgact ttctcagcaa catgtcgatg gacttccaga 60 accacctggg cagctgtaag tgtcgcatac acactatctc tgcctccagc tcctatgggg 120 120 <210> 274 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 274_EGFR <400> 274 accacctggg cagctgtaag tgtcgcatac acactatctc tgcctccagc tcctatgggg 60 gacagctcta cagcactggg gcaggggaga gaagccatgt ttagtaagtc acattaatca 120 120 <210> 275 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 275_EGFR <400> 275 cagtttctca tcatttcact gagatatgca tctattactt ttacatttca ggccaaaagt 60 gtgatccaag ctgtcccaat gggagctgct ggggtgcagg agaggagaac tgccagaaac 120 120 <210> 276 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 276_EGFR <400> 276 gccaaaagtg tgatccaagc tgtcccaatg ggagctgctg gggtgcagga gaggagaact 60 gccagaaacg taagtcagtg aacagcctca gacccatgtg tgaccgcccc tctcttcctt 120 120 <210> 277 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 277_EGFR <400> 277 gtgaccaaaa tcatctgtgc ccagcagtgc tccgggcgct gccgtggcaa gtcccccagt 60 gactgctgcc acaaccagtg tgctgcaggc tgcacaggcc cccgggagag cgactgcctg 120 120 <210> 278 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 278_EGFR <400> 278 tgaccaaaat catctgtgcc cagcagtgct ccgggcgctg ccgtggcaag tcccccagtg 60 actgctgcca caaccagtgt gctgcaggct gcacaggccc ccgggagagc gactgcctgg 120 120 <210> 279 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 279_EGFR <400> 279 ccgtgtgtgg cgctgagtgt acttacctca cttgcccagc gtgtcctctc tcctccatag 60 gtctgccgca aattccgaga cgaagccacg tgcaaggaca cctgcccccc actcatgctc 120 120 <210> 280 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 280_EGFR <400> 280 gtctgccgca aattccgaga cgaagccacg tgcaaggaca cctgcccccc actcatgctc 60 tacaacccca ccacgtacca gatggatgtg aaccccgagg gcaaatacag ctttggtgcc 120 120 <210> 281 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 281_EGFR <400> 281 tacaacccca ccacgtacca gatggatgtg aaccccgagg gcaaatacag ctttggtgcc 60 acctgcgtga agaagtgtcc ccgtgagtcc tcctctgtgg gccctctaac tggtcaggca 120 120 <210> 282 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 282_EGFR <400> 282 acctgcgtga agaagtgtcc ccgtgagtcc tcctctgtgg gccctctaac tggtcaggca 60 tccttgtccc gctctgtctc ctgctgagcc ctggagtatc ccatcttgga gagtctttgg 120 120 <210> 283 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 283_EGFR <400> 283 caggtaatta tgtggtgaca gatcacggct cgtgcgtccg agcctgtggg gccgacagct 60 atgagatgga ggaagacggc gtccgcaagt gtaagaagtg cgaagggcct tgccgcaaag 120 120 <210> 284 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 284_EGFR <400> 284 gtaattatgt ggtgacagat cacggctcgt gcgtccgagc ctgtggggcc gacagctatg 60 agatggagga agacggcgtc cgcaagtgta agaagtgcga agggccttgc cgcaaaggta 120 120 <210> 285 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 285_EGFR <400> 285 ccctagctat tcttaatcca acaaatgtga acggaataca cgtctctctt atctctgcag 60 tgtgtaacgg aataggtatt ggtgaattta aagactcact ctccataaat gctacgaata 120 120 <210> 286 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 286_EGFR <400> 286 tgtgtaacgg aataggtatt ggtgaattta aagactcact ctccataaat gctacgaata 60 ttaaacactt caaaaactgc acctccatca gtggcgatct ccacatcctg ccggtggcat 120 120 <210> 287 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 287_EGFR <400> 287 ttaaacactt caaaaactgc acctccatca gtggcgatct ccacatcctg ccggtggcat 60 ttagggggtg agtcacaggt tcagttgctt gtataaagaa aaacaaaatc tgccttttta 120 120 <210> 288 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 288_EGFR <400> 288 ttagggggtg agtcacaggt tcagttgctt gtataaagaa aaacaaaatc tgccttttta 60 actggtagag attggtgatc aataatcacc ctgttgtttg tttcagtgac tccttcacac 120 120 <210> 289 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 289_EGFR <400> 289 ttggtgatca ataatcaccc tgttgtttgt ttcagtgact ccttcacaca tactcctcct 60 ctggatccac aggaactgga tattctgaaa accgtaaagg aaatcacagg tttgagctga 120 120 <210> 290 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 290_EGFR <400> 290 tgactccttc acacatactc ctcctctgga tccacaggaa ctggatattc tgaaaaccgt 60 aaaggaaatc acaggtttga gctgaattat cacatgaata taaatgggaa atcagtgttt 120 120 <210> 291 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 291_EGFR <400> 291 gtgtctgaag tctttcatct gccttacagg gtttttgctg attcaggctt ggcctgaaaa 60 caggacggac ctccatgcct ttgagaacct agaaatcata cgcggcagga ccaagcaaca 120 120 <210> 292 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 292_EGFR <400> 292 ggtttttgct gattcaggct tggcctgaaa acaggacgga cctccatgcc tttgagaacc 60 tagaaatcat acgcggcagg accaagcaac agtaagttga ccacagccaa agcctggtag 120 120 <210> 293 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 293_EGFR <400> 293 ttcagggata cattgttttt ataatttttc accacatgat ttttcttctc tccaatgtag 60 tggtcagttt tctcttgcag tcgtcagcct gaacataaca tccttgggat tacgctccct 120 120 <210> 294 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 294_EGFR <400> 294 tggtcagttt tctcttgcag tcgtcagcct gaacataaca tccttgggat tacgctccct 60 caaggagata agtgatggag atgtgataat ttcaggaaac aaaaatttgt gctatgcaaa 120 120 <210> 295 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 295_EGFR <400> 295 caaggagata agtgatggag atgtgataat ttcaggaaac aaaaatttgt gctatgcaaa 60 tacaataaac tggaaaaaac tgtttgggac ctccggtcag aaaaccaaaa ttataagcaa 120 120 <210> 296 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 296_EGFR <400> 296 tacaataaac tggaaaaaac tgtttgggac ctccggtcag aaaaccaaaa ttataagcaa 60 cagaggtgaa aacagctgca gtaagtcacc gctttctgtt tagtttatgg agttggttct 120 120 <210> 297 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 297_EGFR <400> 297 cagaggtgaa aacagctgca gtaagtcacc gctttctgtt tagtttatgg agttggttct 60 aatgggtcct ttatttgtat ttagaatatt gaagggctat tcccatttaa attacttttt 120 120 <210> 298 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 298_EGFR <400> 298 ctccggcccc tcgggtccct gctctgtcac tgactgctgt gacccactct gtctccgcag 60 aggccacagg ccaggtctgc catgccttgt gctcccccga gggctgctgg ggcccggagc 120 120 <210> 299 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 299_EGFR <400> 299 aggccacagg ccaggtctgc catgccttgt gctcccccga gggctgctgg ggcccggagc 60 ccagggactg cgtctcttgc cggaatgtca gccgaggcag ggaatgcgtg gacaagtgca 120 120 <210> 300 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 300_EGFR <400> 300 ccagggactg cgtctcttgc cggaatgtca gccgaggcag ggaatgcgtg gacaagtgca 60 accttctgga ggggtaggag gttatttctt taatcccctt gcgttgatca aaaataaggc 120 120 <210> 301 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 301_EGFR <400> 301 accttctgga ggggtaggag gttatttctt taatcccctt gcgttgatca aaaataaggc 60 tccaggttgt tgttatagct ttacaggcat tctgtttgat tttctcttcc ttttattctt 120 120 <210> 302 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 302_EGFR <400> 302 gctgacgggt ttcctcttcc tcctctcagt gagccaaggg agtttgtgga gaactctgag 60 tgcatacagt gccacccaga gtgcctgcct caggccatga acatcacctg cacaggacgg 120 120 <210> 303 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 303_EGFR <400> 303 tgagccaagg gagtttgtgg agaactctga gtgcatacag tgccacccag agtgcctgcc 60 tcaggccatg aacatcacct gcacaggacg ggtaagagcc ccttgctgct atccacgtcc 120 120 <210> 304 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 304_EGFR <400> 304 tccattttga aagagaaaag aaagagacat gcatgaacat ttttctccac cttggtgcag 60 ggaccagaca actgtatcca gtgtgcccac tacattgacg gcccccactg cgtcaagacc 120 120 <210> 305 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 305_EGFR <400> 305 ggaccagaca actgtatcca gtgtgcccac tacattgacg gcccccactg cgtcaagacc 60 tgcccggcag gagtcatggg agaaaacaac accctggtct ggaagtacgc agacgccggc 120 120 <210> 306 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 306_EGFR <400> 306 tgcccggcag gagtcatggg agaaaacaac accctggtct ggaagtacgc agacgccggc 60 catgtgtgcc acctgtgcca tccaaactgc acctacgggt gagtggaaag tgaaggagaa 120 120 <210> 307 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 307_EGFR <400> 307 catgtgtgcc acctgtgcca tccaaactgc acctacgggt gagtggaaag tgaaggagaa 60 cagaacattt cctctcttgc aaattcagag atcaaaaatg tctcccaagt tttccggcaa 120 120 <210> 308 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 308_EGFR <400> 308 cacttacttt gtataagaaa tagtttgcca aatatagaaa gaggggattt agtcaagatt 60 taaattaaaa atgttagtgg tcatttttct aatgtctttc tattttttcc caggtcctaa 120 120 <210> 309 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 309_EGFR <400> 309 gtcctaataa atcttcactg tctgacttta gtctcccact aaaactgcat ttcctttcta 60 caatttcaat ttctcccttt gcttcaaata aagtcctgac actattcatt tgacatatgg 120 120 <210> 310 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 310_EGFR <400> 310 ttacaccagg gctccccagg cctctcacat attgaaatgt acttgtccat ctttctccag 60 gccaggaaat gagagtctca aagccatgtt attctgcctt tttaaactat catcctgtaa 120 120 <210> 311 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 311_EGFR <400> 311 gccaggaaat gagagtctca aagccatgtt attctgcctt tttaaactat catcctgtaa 60 tcaaagtaat gatggcagcg tgtcccacca gagcgggagc ccagctgctc aggagtcatg 120 120 <210> 312 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 312_EGFR <400> 312 tcaaagtaat gatggcagcg tgtcccacca gagcgggagc ccagctgctc aggagtcatg 60 cttaggatgg atcccttctc ttctgccgtc agagtttcag ctgggttggg gtggatgcag 120 120 <210> 313 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 313_EGFR <400> 313 cttaggatgg atcccttctc ttctgccgtc agagtttcag ctgggttggg gtggatgcag 60 ccacctccat gcctggcctt ctgcatctgt gatcatcacg gcctcctcct gccactgagc 120 120 <210> 314 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 314_EGFR <400> 314 ccacctccat gcctggcctt ctgcatctgt gatcatcacg gcctcctcct gccactgagc 60 ctcatgcctt cacgtgtctg ttccccccgc ttttcctttc tgccacccct gcacgtgggc 120 120 <210> 315 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 315_EGFR <400> 315 atgatttaat taaaaatctc caaaatatat gccaaagaag tagaatgaga aaaatgtata 60 tttctctttc acttcctaca gatgcactgg gccaggtctt gaaggctgtc caacgaatgg 120 120 <210> 316 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 316_EGFR <400> 316 atgcactggg ccaggtcttg aaggctgtcc aacgaatggg taagtgttca cagctctgtg 60 tcacatggac ctcgtcaaga atgaccacac tgctgtgggt gaagatgctt tcctgcattt 120 120 <210> 317 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 317_EGFR <400> 317 gccaaggcca tggaatctgt cagcaacctc acccttcctt gttcctccac ctcattccag 60 gcctaagatc ccgtccatcg ccactgggat ggtgggggcc ctcctcttgc tgctggtggt 120 120 <210> 318 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 318_EGFR <400> 318 gcctaagatc ccgtccatcg ccactgggat ggtgggggcc ctcctcttgc tgctggtggt 60 ggccctgggg atcggcctct tcatgcgaag gcgccacatc gttcggaagc gcacgctgcg 120 120 <210> 319 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 319_EGFR <400> 319 ggccctgggg atcggcctct tcatgcgaag gcgccacatc gttcggaagc gcacgctgcg 60 gaggctgctg caggagaggg aggtgagtgc cagtcctggg tgggctcagg agccctcgca 120 120 <210> 320 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 320_EGFR <400> 320 gaggctgctg caggagaggg aggtgagtgc cagtcctggg tgggctcagg agccctcgca 60 ccccgacagg aacaagggcc agccccgaga acgggccatt agcagttgtg tatgttagat 120 120 <210> 321 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 321_EGFR <400> 321 tgctttccag catggtgagg gctgaggtga cccttgtctc tgtgttcttg tcccccccag 60 cttgtggagc ctcttacacc cagtggagaa gctcccaacc aagctctctt gaggatcttg 120 120 <210> 322 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 322_EGFR <400> 322 cttgtggagc ctcttacacc cagtggagaa gctcccaacc aagctctctt gaggatcttg 60 aaggaaactg aattcaaaaa gatcaaagtg ctgggctccg gtgcgttcgg cacggtgtat 120 120 <210> 323 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 323_EGFR <400> 323 aaggaaactg aattcaaaaa gatcaaagtg ctgggctccg gtgcgttcgg cacggtgtat 60 aaggtaaggt ccctggcaca ggcctctggg ctgggccgca gggcctctca tggtctggtg 120 120 <210> 324 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 324_EGFR <400> 324 aaggtaaggt ccctggcaca ggcctctggg ctgggccgca gggcctctca tggtctggtg 60 gggagcccag agtccttgca agctgtatat ttccatcatc tactttactc tttgtttcac 120 120 <210> 325 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 325_EGFR <400> 325 ttccttctct ctctgtcata gggactctgg atcccagaag gtgagaaagt taaaattccc 60 gtcgctatca aggaattaag agaagcaaca tctccgaaag ccaacaagga aatcctcgat 120 120 <210> 326 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 326_EGFR <400> 326 ggactctgga tcccagaagg tgagaaagtt aaaattcccg tcgctatcaa ggaattaaga 60 gaagcaacat ctccgaaagc caacaaggaa atcctcgatg tgagtttctg ctttgctgtg 120 120 <210> 327 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 327_EGFR <400> 327 tgtgcccctc cttctggcca ccatgcgaag ccacactgac gtgcctctcc ctccctccag 60 gaagcctacg tgatggccag cgtggacaac ccccacgtgt gccgcctgct gggcatctgc 120 120 <210> 328 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 328_EGFR <400> 328 gaagcctacg tgatggccag cgtggacaac ccccacgtgt gccgcctgct gggcatctgc 60 ctcacctcca ccgtgcagct catcacgcag ctcatgccct tcggctgcct cctggactat 120 120 <210> 329 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 329_EGFR <400> 329 ctcacctcca ccgtgcagct catcacgcag ctcatgccct tcggctgcct cctggactat 60 gtccgggaac acaaagacaa tattggctcc cagtacctgc tcaactggtg tgtgcagatc 120 120 <210> 330 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 330_EGFR <400> 330 gtccgggaac acaaagacaa tattggctcc cagtacctgc tcaactggtg tgtgcagatc 60 gcaaaggtaa tcagggaagg gagatacggg gaggggagat aaggagccag gatcctcaca 120 120 <210> 331 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 331_EGFR <400> 331 gcaaaggtaa tcagggaagg gagatacggg gaggggagat aaggagccag gatcctcaca 60 tgcggtctgc gctcctggga tagcaagagt ttgccatggg gatatgtgtg tgcgtgcatg 120 120 <210> 332 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 332_EGFR <400> 332 ggatgcagag cttcttccca tgatgatctg tccctcacag cagggtcttc tctgtttcag 60 ggcatgaact acttggagga ccgtcgcttg gtgcaccgcg acctggcagc caggaacgta 120 120 <210> 333 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 333_EGFR <400> 333 ggcatgaact acttggagga ccgtcgcttg gtgcaccgcg acctggcagc caggaacgta 60 ctggtgaaaa caccgcagca tgtcaagatc acagattttg ggctggccaa actgctgggt 120 120 <210> 334 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 334_EGFR <400> 334 ctggtgaaaa caccgcagca tgtcaagatc acagattttg ggctggccaa actgctgggt 60 gcggaagaga aagaatacca tgcagaagga ggcaaagtaa ggaggtggct ttaggtcagc 120 120 <210> 335 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 335_EGFR <400> 335 gcggaagaga aagaatacca tgcagaagga ggcaaagtaa ggaggtggct ttaggtcagc 60 cagcattttc ctgacaccag ggaccaggct gccttcccac tagctgtatt gtttaacaca 120 120 <210> 336 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 336_EGFR <400> 336 gaaactaata gttgtctcac tgcctcatct ctcaccatcc caaggtgcct atcaagtgga 60 tggcattgga atcaatttta cacagaatct atacccacca gagtgatgtc tggagctacg 120 120 <210> 337 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 337_EGFR <400> 337 gtgcctatca agtggatggc attggaatca attttacaca gaatctatac ccaccagagt 60 gatgtctgga gctacggtga gtcataatcc tgatgctaat gagtttgtac tgaggccaag 120 120 <210> 338 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 338_EGFR <400> 338 agggattgtg attgttcatt catgatccca ctgccttctt ttcttgcttc atcctctcag 60 gggtgactgt ttgggagttg atgacctttg gatccaagcc atatgacgga atccctgcca 120 120 <210> 339 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 339_EGFR <400> 339 gggtgactgt ttgggagttg atgacctttg gatccaagcc atatgacgga atccctgcca 60 gcgagatctc ctccatcctg gagaaaggag aacgcctccc tcagccaccc atatgtacca 120 120 <210> 340 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 340_EGFR <400> 340 gcgagatctc ctccatcctg gagaaaggag aacgcctccc tcagccaccc atatgtacca 60 tcgatgtcta catgatcatg gtcaagtgtg agtgactggt gggtctgtcc acactgccta 120 120 <210> 341 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 341_EGFR <400> 341 tcgatgtcta catgatcatg gtcaagtgtg agtgactggt gggtctgtcc acactgccta 60 gctgagcctt ggtggctgct cttagccaaa cagctgaggc ctttgcatcc ctggagaaat 120 120 <210> 342 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 342_EGFR <400> 342 ttttttctca ttccttcccc aggctggatg atagacgcag atagtcgccc aaagttccgt 60 gagttgatca tcgaattctc caaaatggcc cgagaccccc agcgctacct tgtcattcag 120 120 <210> 343 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 343_EGFR <400> 343 gctggatgat agacgcagat agtcgcccaa agttccgtga gttgatcatc gaattctcca 60 aaatggcccg agacccccag cgctaccttg tcattcaggt acaaattgca gtctgtgctt 120 120 <210> 344 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 344_EGFR <400> 344 ccaagaagtg gaatagcatc tctacgggcc attctaatag cctcaaaatc tctgcaccag 60 ggggatgaaa gaatgcattt gccaagtcct acagactcca acttctaccg tgccctgatg 120 120 <210> 345 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 345_EGFR <400> 345 ggggatgaaa gaatgcattt gccaagtcct acagactcca acttctaccg tgccctgatg 60 gatgaagaag acatggacga cgtggtggat gccgacgagt acctcatccc acagcagggc 120 120 <210> 346 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 346_EGFR <400> 346 gatgaagaag acatggacga cgtggtggat gccgacgagt acctcatccc acagcagggc 60 ttcttcagca gcccctccac gtcacggact cccctcctga gctctctggt atgaaatctc 120 120 <210> 347 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 347_EGFR <400> 347 ttcttcagca gcccctccac gtcacggact cccctcctga gctctctggt atgaaatctc 60 tgtctctctc tctctctcaa gctgtgtcta ctcatttgaa caaattgaat tttagggaaa 120 120 <210> 348 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 348_EGFR <400> 348 acctgcattc aggaaaagtg gatgagatgt ggtacaagca ttccatgggc aacttctctg 60 tttctttttc agagtgcaac cagcaacaat tccaccgtgg cttgcattga tagaaatggg 120 120 <210> 349 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 349_EGFR <400> 349 agtgcaacca gcaacaattc caccgtggct tgcattgata gaaatggggt atgtatgaac 60 accttataag ccagaattta cagctctcca ctatggctct attttacatg gaaaatgcct 120 120 <210> 350 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 350_EGFR <400> 350 tcctcctgca gctgcaaagc tgtcccatca aggaagacag cttcttgcag cgatacagct 60 cagaccccac aggcgccttg actgaggaca gcatagacga caccttcctc ccagtgcctg 120 120 <210> 351 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 351_EGFR <400> 351 ctgcaaagct gtcccatcaa ggaagacagc ttcttgcagc gatacagctc agaccccaca 60 ggcgccttga ctgaggacag catagacgac accttcctcc cagtgcctgg tgagtggctt 120 120 <210> 352 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 352_EGFR <400> 352 gatcctgcat gggatggtgc tttgctgatt acttcacctc tgatttcttt ccactttcag 60 aatacataaa ccagtccgtt cccaaaaggc ccgctggctc tgtgcagaat cctgtctatc 120 120 <210> 353 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 353_EGFR <400> 353 aatacataaa ccagtccgtt cccaaaaggc ccgctggctc tgtgcagaat cctgtctatc 60 acaatcagcc tctgaacccc gcgcccagca gagacccaca ctaccaggac ccccacagca 120 120 <210> 354 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 354_EGFR <400> 354 acaatcagcc tctgaacccc gcgcccagca gagacccaca ctaccaggac ccccacagca 60 ctgcagtggg caaccccgag tatctcaaca ctgtccagcc cacctgtgtc aacagcacat 120 120 <210> 355 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 355_EGFR <400> 355 ctgcagtggg caaccccgag tatctcaaca ctgtccagcc cacctgtgtc aacagcacat 60 tcgacagccc tgcccactgg gcccagaaag gcagccacca aattagcctg gacaaccctg 120 120 <210> 356 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 356_EGFR <400> 356 tcgacagccc tgcccactgg gcccagaaag gcagccacca aattagcctg gacaaccctg 60 actaccagca ggacttcttt cccaaggaag ccaagccaaa tggcatcttt aagggctcca 120 120 <210> 357 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 357_EGFR <400> 357 actaccagca ggacttcttt cccaaggaag ccaagccaaa tggcatcttt aagggctcca 60 cagctgaaaa tgcagaatac ctaagggtcg cgccacaaag cagtgaattt attggagcat 120 120 <210> 358 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 358_EGFR <400> 358 cagctgaaaa tgcagaatac ctaagggtcg cgccacaaag cagtgaattt attggagcat 60 gaccacggag gatagtatga gccctaaaaa tccagactct ttcgataccc aggaccaagc 120 120 <210> 359 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 359_EGFR <400> 359 gaccacggag gatagtatga gccctaaaaa tccagactct ttcgataccc aggaccaagc 60 cacagcaggt cctccatccc aacagccatg cccgcattag ctcttagacc cacagactgg 120 120 <210> 360 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 360_BRAF <400> 360 tgatgttaac aaattgtacg aacacaagac ttaagaaata agagcagatg ctgccatgat 60 ggtggctact tgaaggctgc aaattctcct gtagagggag gacaagagct aattttaaaa 120 120 <210> 361 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 361_BRAF <400> 361 agaaataaga gcagatgctg ccatgatggt ggctacttga aggctgcaaa ttctcctgta 60 gagggaggac aagagctaat tttaaaaaag tcatctcaaa taacctagag acacagaaaa 120 120 <210> 362 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 362_BRAF <400> 362 acatatgttc atttattttc cttttgttgc tactctcctg aactctctca ctcatttgtt 60 tcagtggaca ggaaacgcac catatccccc tgcctggatg ggtgtttttg gagaagcaca 120 120 <210> 363 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 363_BRAF <400> 363 tcagtggaca ggaaacgcac catatccccc tgcctggatg ggtgtttttg gagaagcaca 60 agcatataga ctaaaatcct ctgtttggaa accagcccga ttcaaggagg gttctgatgc 120 120 <210> 364 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 364_BRAF <400> 364 agcatataga ctaaaatcct ctgtttggaa accagcccga ttcaaggagg gttctgatgc 60 actgcggtga atttttggca atgagcgggc cagcagctca atagaggcga gaatctacaa 120 120 <210> 365 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 365_BRAF <400> 365 actgcggtga atttttggca atgagcgggc cagcagctca atagaggcga gaatctacaa 60 aaaaaaaaag aaaaaaaaaa gaaaaaaaaa gaaaaaagaa aaaaaaagaa agaaagaaaa 120 120 <210> 366 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 366_BRAF <400> 366 tcagaaatct gtctatgaat gttagtctgt tcttttggat agcatgaagc ttttacttac 60 ttggggaaag agtggtctct catctctttt ctttttgagg cactctgcca ttaatctctt 120 120 <210> 367 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 367_BRAF <400> 367 ttggggaaag agtggtctct catctctttt ctttttgagg cactctgcca ttaatctctt 60 catggctttt ggacagttac tccgtacctt actgagatct ggagacaggt atcctcgtcc 120 120 <210> 368 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 368_BRAF <400> 368 catggctttt ggacagttac tccgtacctt actgagatct ggagacaggt atcctcgtcc 60 caccataaaa attatctgga gagagaaaaa aaagggaaat aattcaacct tgtagataag 120 120 <210> 369 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 369_BRAF <400> 369 caccataaaa attatctgga gagagaaaaa aaagggaaat aattcaacct tgtagataag 60 ttgaaaaata tacttcacac tcattgaaaa cacaataagc tgtacattta cagcttacga 120 120 <210> 370 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 370_BRAF <400> 370 tacaactgga gccttgtata tagacggtaa aataaacacc aagacgtggt aaatatttac 60 ctggtccctg ttgttgatgt ttgaataagg taactgtcca gtcatcaatt catacagaac 120 120 <210> 371 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 371_BRAF <400> 371 ctggtccctg ttgttgatgt ttgaataagg taactgtcca gtcatcaatt catacagaac 60 aattccaaat gcatatacat ctgactgaaa gctgtatgga tttttatctt gcattctgat 120 120 <210> 372 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 372_BRAF <400> 372 aattccaaat gcatatacat ctgactgaaa gctgtatgga tttttatctt gcattctgat 60 gacttctggt gcctgttaga acatacaaag aaaaatattc ttcacttcaa ttgaataaag 120 120 <210> 373 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 373_BRAF <400> 373 gacttctggt gcctgttaga acatacaaag aaaaatattc ttcacttcaa ttgaataaag 60 actgaaaaac aacctactat aattcctaga gcaatgcttt taccattaaa acacctgtct 120 120 <210> 374 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 374_BRAF <400> 374 ccatccacaa aatggatcca gacaactgtt caaactgatg ggacccactc catcgagatt 60 tcactgtagc tagaccaaaa tcacctattt ttactgtgag gtcttcatga agaaatatat 120 120 <210> 375 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 375_BRAF <400> 375 catccacaaa atggatccag acaactgttc aaactgatgg gacccactcc atcgagattt 60 cactgtagct agaccaaaat cacctatttt tactgtgagg tcttcatgaa gaaatatatc 120 120 <210> 376 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 376_BRAF <400> 376 aatgtgaaga caaaatgcag aagaaaaagt caggatgttt tcaaacttcg cagacaaatt 60 tcaggaagga tactattact cttgaggtct ctgtggatga ttgacttggc gtgtaagtaa 120 120 <210> 377 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 377_BRAF <400> 377 tattactctt gaggtctctg tggatgattg acttggcgtg taagtaactg aaaaacaaaa 60 catcatttta acctgagtag ggctaaagga ctctggcctc gaaatctaca gaacatactt 120 120 <210> 378 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 378_BRAF <400> 378 taaaacatcc tcaatggtct tcaaaaataa tttacaagac atttaacgaa tggaacttac 60 tccatgccct gtgcagtctg tcgtgcaata tctataagtt tgatcatctc aaatttggtc 120 120 <210> 379 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 379_BRAF <400> 379 tccatgccct gtgcagtctg tcgtgcaata tctataagtt tgatcatctc aaatttggtc 60 tcaatgatat ggagatggtg atacaagctg gagccctcac accactgggt aacaatagcc 120 120 <210> 380 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 380_BRAF <400> 380 tcaatgatat ggagatggtg atacaagctg gagccctcac accactgggt aacaatagcc 60 agttgtggct ttgtggaata gcccatgaag agtaggatat tcacatgtcg tgttttcctg 120 120 <210> 381 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 381_BRAF <400> 381 agttgtggct ttgtggaata gcccatgaag agtaggatat tcacatgtcg tgttttcctg 60 tacaaagaaa tgtgacagta aacattaaat gtcgacaaac tttagcaatt cttacaaaag 120 120 <210> 382 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 382_BRAF <400> 382 ctttctctgg aaaagagtaa ttcacacaag ctcacctgag tactcctact tcatttttga 60 aggcttgtaa ctgctgaggt gtaggtgctg tcacattcaa cattttcact gccacatcac 120 120 <210> 383 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 383_BRAF <400> 383 ctgagtactc ctacttcatt tttgaaggct tgtaactgct gaggtgtagg tgctgtcaca 60 ttcaacattt tcactgccac atcacctaaa aggcaattgt tactccaagt gtcatttcaa 120 120 <210> 384 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 384_BRAF <400> 384 accatgccac tttcccttgt agactgttcc aaatgatcca gatccaattc tttgtcccac 60 tgtaatctgc ccatcaggaa tctcccaatc atcactcgag tcccgtctac caagtgtttt 120 120 <210> 385 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 385_BRAF <400> 385 catgccactt tcccttgtag actgttccaa atgatccaga tccaattctt tgtcccactg 60 taatctgccc atcaggaatc tcccaatcat cactcgagtc ccgtctacca agtgttttct 120 120 <210> 386 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 386_BRAF <400> 386 tttggctgtg acttctaaga agaaagaatt cagagaaaaa aagatatcat atactcttac 60 cattcgattc ctgtcttctg aggatgaaga tgacttcctt tctcgctgag gtcctggaga 120 120 <210> 387 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 387_BRAF <400> 387 cattcgattc ctgtcttctg aggatgaaga tgacttcctt tctcgctgag gtcctggaga 60 tttctgtaag gctttcacgt tagttagtga gccaggtaat gaggcagggg gggtagcaga 120 120 <210> 388 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 388_BRAF <400> 388 tttctgtaag gctttcacgt tagttagtga gccaggtaat gaggcagggg gggtagcaga 60 caaacctgtg gttgatccta aattagtgaa aagaaaaatg tatacattaa ggaggagcaa 120 120 <210> 389 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 389_BRAF <400> 389 caaacctgtg gttgatccta aattagtgaa aagaaaaatg tatacattaa ggaggagcaa 60 gtatgttaat ttatcagggg tagaaggttg ggggatattt agacttaatt ttaaaatgta 120 120 <210> 390 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 390_BRAF <400> 390 aaagaggcaa gtataaagga aataagcagc aaagcaattg cagtttcctt gagtttttaa 60 aaaaacctga aatcactact tacctccatc accacgaaat ccttggtctc taatcaagtc 120 120 <210> 391 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 391_BRAF <400> 391 ctccatcacc acgaaatcct tggtctctaa tcaagtccta caaataaata gtaatgtata 60 tttattccaa gcaagcatat aatcagagag tagcgataac actgaatttt ccactaacgt 120 120 <210> 392 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 392_BRAF <400> 392 gcagaaaaat aaagatacat acttggtttt tttttagttc tagcaatgct ggatacttac 60 atcaatattg acaggttcta ttgtgtttat atgcacattg ggagctgatg aggatcggtc 120 120 <210> 393 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 393_BRAF <400> 393 atcaatattg acaggttcta ttgtgtttat atgcacattg ggagctgatg aggatcggtc 60 tcgttgccca aattgatttc gatgatcttc atctgctggt cggaagggct gtggaattgg 120 120 <210> 394 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 394_BRAF <400> 394 tcgttgccca aattgatttc gatgatcttc atctgctggt cggaagggct gtggaattgg 60 aatggatttt gaaggagacg gactggtgag aatttggggc ctggaaaaat gaagtcattg 120 120 <210> 395 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 395_BRAF <400> 395 aatggatttt gaaggagacg gactggtgag aatttggggc ctggaaaaat gaagtcattg 60 gaagataaga ttcagagtaa cgatataaag gtaataatat ttaaaaagga agataaaagg 120 120 <210> 396 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 396_BRAF <400> 396 gagatccaaa agaaagcggt tcaagtagca tgtcgcccaa gagcagaagt caaaccatac 60 ccaatagagt ccgaggcggg tgcggaaggg gatgatccag atgttagggc agtctctgct 120 120 <210> 397 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 397_BRAF <400> 397 ccaatagagt ccgaggcggg tgcggaaggg gatgatccag atgttagggc agtctctgct 60 aaggacgcct cttcctgtgg tattgggtgg tgttcaaaga acttggagac aaacagcaaa 120 120 <210> 398 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 398_BRAF <400> 398 aaggacgcct cttcctgtgg tattgggtgg tgttcaaaga acttggagac aaacagcaaa 60 ctgtgaggca aaacaaaaca aacctaactt gtgcaaaacc cagaagcttc atataccaaa 120 120 <210> 399 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 399_BRAF <400> 399 cattaagaaa atttaagtgt aaaatggtag gtagaaaaga gatatttttg gattacttac 60 tcaagttggt cataattaac acacatcagt ggaacttctg tactacaacg ctggtgaaat 120 120 <210> 400 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 400_BRAF <400> 400 tcaagttggt cataattaac acacatcagt ggaacttctg tactacaacg ctggtgaaat 60 ttataaccac atgtttgaca gcggaaaccc tggaaaagca gctttcgaca aaagtcacaa 120 120 <210> 401 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 401_BRAF <400> 401 ttataaccac atgtttgaca gcggaaaccc tggaaaagca gctttcgaca aaagtcacaa 60 aatgctaagg tgaaaaacgt ttttcgtacc tgcaaagtaa aaaatcacag agatttcaaa 120 120 <210> 402 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 402_BRAF <400> 402 aatgctaagg tgaaaaacgt ttttcgtacc tgcaaagtaa aaaatcacag agatttcaaa 60 aactcacaag aaaactttct agaaactgac gtatctactc tcttgtttaa aataacaaag 120 120 <210> 403 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 403_BRAF <400> 403 aatgtaaaga tacatacaaa gttgtgtgtt gtaagtggaa cattctccaa cacttccaca 60 tgcaattctt ctccagtaag ccaggaaata tcagtgtccc aaccaattgg tttcttctct 120 120 <210> 404 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 404_BRAF <400> 404 aaagttgtgt gttgtaagtg gaacattctc caacacttcc acatgcaatt cttctccagt 60 aagccaggaa atatcagtgt cccaaccaat tggtttcttc tctctgaaaa atgtagacac 120 120 <210> 405 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 405_BRAF <400> 405 cacatacaaa ccatacccat cctgaattct gtaaacagca cagcactctg ggattagacc 60 tctcatcatc agtgctttct ttagactgtc tcggactgta actccacacc ttgcaggtac 120 120 <210> 406 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 406_BRAF <400> 406 ccatcctgaa ttctgtaaac agcacagcac tctgggatta gacctctcat catcagtgct 60 ttctttagac tgtctcggac tgtaactcca caccttgcag gtacctatgg tatcataaat 120 120 <210> 407 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 407_BRAF <400> 407 aactgatctg tctgaaaaat acaaagaaac agcaaaatgg tgatattaaa actgactcac 60 cactgtcctc tgtttgttgg gcaggaagac tctaacgata ggtttttgtg gtgacttggg 120 120 <210> 408 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 408_BRAF <400> 408 cactgtcctc tgtttgttgg gcaggaagac tctaacgata ggtttttgtg gtgacttggg 60 gttgctccgt gccacatctg tgggattttg aaaaactgaa agagatgaag gtagcactga 120 120 <210> 409 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 409_BRAF <400> 409 gttgctccgt gccacatctg tgggattttg aaaaactgaa agagatgaag gtagcactga 60 aaggctagaa gaggaagaag atgtaacggt atccattgat gcagagctag aaacagaaaa 120 120 <210> 410 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 410_BRAF <400> 410 aaggctagaa gaggaagaag atgtaacggt atccattgat gcagagctag aaacagaaaa 60 atcagttccg ttccccagag attccaataa ctgttgttct ctttgttgga gtgcatctag 120 120 <210> 411 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 411_BRAF <400> 411 atcagttccg ttccccagag attccaataa ctgttgttct ctttgttgga gtgcatctag 60 cttgctggtg tattcttcat aggcctataa aataaagcag acttatattc aatccggact 120 120 <210> 412 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 412_BRAF <400> 412 cttgctggtg tattcttcat aggcctataa aataaagcag acttatattc aatccggact 60 ttgtcctgac attaacaaaa gagaatataa aattttagcc tttgattata atcttttcac 120 120 <210> 413 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 413_BRAF <400> 413 tgatactcaa aagcttacct ccagatatat tgatggtgga ttatgctccc caccaaattt 60 gtccaatagg gcctctatat gttcctgtgt caacttaatc atttgtttga tattccacac 120 120 <210> 414 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 414_BRAF <400> 414 ctccagatat attgatggtg gattatgctc cccaccaaat ttgtccaata gggcctctat 60 atgttcctgt gtcaacttaa tcatttgttt gatattccac acctaaaaaa tatttcaaaa 120 120 <210> 415 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 415_BRAF <400> 415 aacaccagcc agccgccgag cccggagtcg ggagggcggc agggtggcgc cagcactcac 60 ctcctccgga atggcagggt ccgcagccga agaggccgcg gcgccggcgc cggcgccggc 120 120 <210> 416 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 416_BRAF <400> 416 ctcctccgga atggcagggt ccgcagccga agaggccgcg gcgccggcgc cggcgccggc 60 ctcgggctcc atgtccccgt tgaacagagc ctggcccggc tccgcgccgc caccaccgcc 120 120 <210> 417 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 417_BRAF <400> 417 ctcgggctcc atgtccccgt tgaacagagc ctggcccggc tccgcgccgc caccaccgcc 60 accgctcagc gccgccatct tataaccgag agccggggcc cgagcggccg ctgtcgggcg 120 120 <210> 418 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 418_BRAF <400> 418 accgctcagc gccgccatct tataaccgag agccggggcc cgagcggccg ctgtcgggcg 60 gggaggggga agggaggcgg agagctgggg gaggcggagg cggaggcgga ggcggaggag 120 120 <210> 419 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 419_PTEN <400> 419 ggtgacgaca cctcccgctc ctggagcgga gggaagaagc ggtgacagcg gtgccagcgg 60 cagctgcagc tccagggagg ggatctgagt cgcttgtcac catttccagg catgggaacg 120 120 <210> 420 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 420_PTEN <400> 420 ctggagcggg agggagaagc ggtggcgacg gtggccacga cggctgcagc tccaaggagg 60 ggatctgagt cgcttgtcac catttccagg gttgggaacg ctggagagtt ggtctctccc 120 120 <210> 421 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 421_PTEN <400> 421 cggctgcagc tccagggagg gggtctgagt cgcctgtcac catttccagg gctgggaacg 60 ccggagagtt ggtctctccc cttctactgc ctccaacacg gcggcggcgg cggctggcac 120 120 <210> 422 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 422_PTEN <400> 422 ccgaagagtt ggtctctcct cttctactgc ctccaacacg gtggcagcag cgactggcac 60 atccagggac ccaggctggt tttaaacctc ccatgcgtcg ctgccacacc ctccatggct 120 120 <210> 423 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 423_PTEN <400> 423 atccagggac ccaggctggt tttaaacctc ccatgcgtcg tcgccacacc ctccgtggct 60 cggactccga aggctgccag cgaaggcagc cattcgaagg attattcgtc ttctccctat 120 120 <210> 424 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 424_PTEN <400> 424 cgggctccgg aggccgccgg cggaggcagc cgttcggagg attattcgtc ttctccccat 60 tccgctgccg ccgctgccag gcctctggct gctgaggaga agcaggccca gtcgctgcaa 120 120 <210> 425 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 425_PTEN <400> 425 tccgctgccg ccgctgccag gcctctggct gctgaggaga agcaggccca gtcgctgcaa 60 ccatccagca gccgccgcag cagccattac ccggctgcgg tccagagcca agcggcggca 120 120 <210> 426 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 426_PTEN <400> 426 ccatccagca gccgccgcag cagccattac ccggctgcgg tccagagcca agcggcggca 60 gagcgagggg catcagctac cgccaagtcc agagccattt ccatcctgca gaagaagccc 120 120 <210> 427 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 427_PTEN <400> 427 gagcgagggg catcagctac cgccaagtcc agagccattt ccatcctgca gaagaagccc 60 cgccaccagc agcttctgcc atctctctcc tcctttttct tcagccacag gctcccagac 120 120 <210> 428 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 428_PTEN <400> 428 cgccaccagc agcttctgcc atctctctcc tcctttttct tcagccacag gctcccagac 60 atgacagcca tcatcaaaga gatcgttagc agaaacaaaa ggagatatca agaggatgga 120 120 <210> 429 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 429_PTEN <400> 429 catctctctc ctcctttttc ttcagccaca ggctcccaga catgacagcc atcatcaaag 60 agatcgttag cagaaacaaa aggagatatc aagaggatgg attcgactta gacttgacct 120 120 <210> 430 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 430_PTEN <400> 430 atgacagcca tcatcaaaga gatcgttagc agaaacaaaa ggagatatca agaggatgga 60 ttcgacttag acttgacctg tatccatttc tgcggctgct cctctttacc tttctgtcac 120 120 <210> 431 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 431_PTEN <400> 431 tttcagatat ttctttcctt aactaaagta ctcagatatt tatccaaaca ttattgctat 60 gggatttcct gcagaaagac ttgaaggcgt atacaggaac aatattgatg atgtagtaag 120 120 <210> 432 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 432_PTEN <400> 432 atatttatcc aaacattatt gctatgggat ttcctgcaga aagacttgaa ggcgtataca 60 ggaacaatat tgatgatgta gtaaggtaag aatgctttga ttttctattt caaatattga 120 120 <210> 433 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 433_PTEN <400> 433 atagtattaa tgtaatttca aatgttagct catttttgtt aatggtggct ttttgtttgt 60 ttgttttgtt ttaaggtttt tggattcaaa gcataaaaac cattacaaga tatacaatct 120 120 <210> 434 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 434_PTEN <400> 434 gtttttggat tcaaagcata aaaaccatta caagatatac aatctgtaag tatgttttct 60 tatttgtatg cttgcaaata tcttctaaaa caactattaa gtgaaagtta tctgcttgtt 120 120 <210> 435 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 435_PTEN <400> 435 tttgttagta ttagtacttt tttttcttcc taagtgcaaa agataacttt atatcacttt 60 taaacttttc ttttagttgt gctgaaagac attatgacac cgccaaattt aattgcagag 120 120 <210> 436 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 436_PTEN <400> 436 ttgtgctgaa agacattatg acaccgccaa atttaattgc agaggtaggt atgaatgtac 60 tgtactatgt tgtataactt aaacccgata gactgtatct tactgtcata acaataatga 120 120 <210> 437 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 437_PTEN <400> 437 ttgttaatta aaaattcaag agtttttttt tcttattctg aggttatctt tttaccacag 60 ttgcacaata tccttttgaa gaccataacc caccacagct agaacttatc aaaccctttt 120 120 <210> 438 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 438_PTEN <400> 438 ttgcacaata tccttttgaa gaccataacc caccacagct agaacttatc aaaccctttt 60 gtgaagatct tgaccaatgg ctaagtgaag atgacaatca tgttgcagca attcactgta 120 120 <210> 439 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 439_PTEN <400> 439 gtgaagatct tgaccaatgg ctaagtgaag atgacaatca tgttgcagca attcactgta 60 aagctggaaa gggacgaact ggtgtaatga tatgtgcata tttattacat cggggcaaat 120 120 <210> 440 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 440_PTEN <400> 440 aagctggaaa gggacgaact ggtgtaatga tatgtgcata tttattacat cggggcaaat 60 ttttaaaggc acaagaggcc ctagatttct atggggaagt aaggaccaga gacaaaaagg 120 120 <210> 441 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 441_PTEN <400> 441 ttttaaaggc acaagaggcc ctagatttct atggggaagt aaggaccaga gacaaaaagg 60 taagttattt tttgatgttt ttcctttcct cttcctggat ctgagaattt attggaaaac 120 120 <210> 442 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 442_PTEN <400> 442 aaataactat aatggaacat tttttttcaa tttggcttct cttttttttc tgtccaccag 60 ggagtaacta ttcccagtca gaggcgctat gtgtattatt atagctacct gttaaagaat 120 120 <210> 443 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 443_PTEN <400> 443 ggagtaacta ttcccagtca gaggcgctat gtgtattatt atagctacct gttaaagaat 60 catctggatt atagaccagt ggcactgttg tttcacaaga tgatgtttga aactattcca 120 120 <210> 444 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 444_PTEN <400> 444 catctggatt atagaccagt ggcactgttg tttcacaaga tgatgtttga aactattcca 60 atgttcagtg gcggaacttg cagtaagtgc ttgaaattct catccttcca tgtattggaa 120 120 <210> 445 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 445_PTEN <400> 445 atgttcagtg gcggaacttg cagtaagtgc ttgaaattct catccttcca tgtattggaa 60 cagttttctt aaccatatct agaagtttac ataaaaattt agaaagaaat ttaccacatt 120 120 <210> 446 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 446_PTEN <400> 446 cagtttgaca gttaaaggca tttcctgtga aataatactg gtatgtattt aaccatgcag 60 atcctcagtt tgtggtctgc cagctaaagg tgaagatata ttcctccaat tcaggaccca 120 120 <210> 447 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 447_PTEN <400> 447 atcctcagtt tgtggtctgc cagctaaagg tgaagatata ttcctccaat tcaggaccca 60 cacgacggga agacaagttc atgtactttg agttccctca gccgttacct gtgtgtggtg 120 120 <210> 448 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 448_PTEN <400> 448 cacgacggga agacaagttc atgtactttg agttccctca gccgttacct gtgtgtggtg 60 atatcaaagt agagttcttc cacaaacaga acaagatgct aaaaaaggtt tgtactttac 120 120 <210> 449 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 449_PTEN <400> 449 atatcaaagt agagttcttc cacaaacaga acaagatgct aaaaaaggtt tgtactttac 60 tttcattggg agaaatatcc aaaataagga cagattaaaa gctatatttt attttatgac 120 120 <210> 450 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 450_PTEN <400> 450 aacatcatta attaaatatg tcatttcatt tctttttctt ttcttttttt ttttttttag 60 gacaaaatgt ttcacttttg ggtaaataca ttcttcatac caggaccaga ggaaacctca 120 120 <210> 451 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 451_PTEN <400> 451 gacaaaatgt ttcacttttg ggtaaataca ttcttcatac caggaccaga ggaaacctca 60 gaaaaagtag aaaatggaag tctatgtgat caagaaatcg atagcatttg cagtatagag 120 120 <210> 452 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 452_PTEN <400> 452 gaaaaagtag aaaatggaag tctatgtgat caagaaatcg atagcatttg cagtatagag 60 cgtgcagata atgacaagga atatctagta cttactttaa caaaaaatga tcttgacaaa 120 120 <210> 453 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 453_PTEN <400> 453 cgtgcagata atgacaagga atatctagta cttactttaa caaaaaatga tcttgacaaa 60 gcaaataaag acaaagccaa ccgatacttt tctccaaatt ttaaggtcag ttaaattaaa 120 120 <210> 454 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 454_PTEN <400> 454 gcaaataaag acaaagccaa ccgatacttt tctccaaatt ttaaggtcag ttaaattaaa 60 cattttgtgg gggttgttga cttgtatgta tgtgatgtgt gtttaattct aggagtacag 120 120 <210> 455 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 455_PTEN <400> 455 actaaatagt ttaagatgag tcatatttgt gggttttcat tttaaatttt ctttctctag 60 gtgaagctgt acttcacaaa aacagtagag gagccgtcaa atccagaggc tagcagttca 120 120 <210> 456 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 456_PTEN <400> 456 gtgaagctgt acttcacaaa aacagtagag gagccgtcaa atccagaggc tagcagttca 60 acttctgtaa caccagatgt tagtgacaat gaacctgatc attatagata ttctgacacc 120 120 <210> 457 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 457_PTEN <400> 457 acttctgtaa caccagatgt tagtgacaat gaacctgatc attatagata ttctgacacc 60 actgactctg atccagagaa tgaacctttt gatgaagatc agcatacaca aattacaaaa 120 120 <210> 458 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 458_PTEN <400> 458 actgactctg atccagagaa tgaacctttt gatgaagatc agcatacaca aattacaaaa 60 gtctgaattt ttttttatca agagggataa aacaccatga aaataaactt gaataaactg 120 120 <210> 459 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 459_PTEN <400> 459 gtctgaattt ttttttatca agagggataa aacaccatga aaataaactt gaataaactg 60 aaaatggacc tttttttttt taatggcaat aggacattgt gtcagattac cagttatagg 120 120 <210> 460 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 460_KRAS <400> 460 tatttacata attacacact ttgtctttga cttctttttc ttctttttac catctttgct 60 catcttttct ttatgttttc gaatttctcg aactaatgta tagaaggcat catcaacacc 120 120 <210> 461 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 461_KRAS <400> 461 ttacataatt acacactttg tctttgactt ctttttcttc tttttaccat ctttgctcat 60 cttttcttta tgttttcgaa tttctcgaac taatgtatag aaggcatcat caacaccctg 120 120 <210> 462 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 462_KRAS <400> 462 ttgttacctt taaaagacat ctgctttctg ccaaaattaa tgtgctgaac ttaaacttac 60 cagattacat tataatgcat tttttaattt tcacacagcc aggagtcttt tcttctttgc 120 120 <210> 463 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 463_KRAS <400> 463 cagattacat tataatgcat tttttaattt tcacacagcc aggagtcttt tcttctttgc 60 tgattttttt caatctgtat tgtcggatct ccctcaccaa tgtataaaaa gcatcctcca 120 120 <210> 464 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 464_KRAS <400> 464 tgattttttt caatctgtat tgtcggatct ccctcaccaa tgtataaaaa gcatcctcca 60 ctctctgcat tgtaaaacac aacttcttta aagtctgttg cattggtaag agtaatttac 120 120 <210> 465 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 465_KRAS <400> 465 ctctctgcat tgtaaaacac aacttcttta aagtctgttg cattggtaag agtaatttac 60 tgggaaagcc atgtgcaaga agtttgagat tatgagcttg agattttttt ttttttaaac 120 120 <210> 466 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 466_KRAS <400> 466 atgacataac agttatgatt ttgcagaaaa cagatctgta tttatttcag tgttacttac 60 ctgtcttgtc tttgctgatg tttcaataaa aggaattcca taacttcttg ctaagtcctg 120 120 <210> 467 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 467_KRAS <400> 467 ctgtcttgtc tttgctgatg tttcaataaa aggaattcca taacttcttg ctaagtcctg 60 agcctgtttt gtgtctactg ttctagaagg caaatcacat ttatttccta ctaggaccat 120 120 <210> 468 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 468_KRAS <400> 468 agcctgtttt gtgtctactg ttctagaagg caaatcacat ttatttccta ctaggaccat 60 aggtacatct tcagagtcct taactctttt aatttgttct ctgggaaaga aaaaaaagtt 120 120 <210> 469 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 469_KRAS <400> 469 aggtacatct tcagagtcct taactctttt aatttgttct ctgggaaaga aaaaaaagtt 60 atagcacagt cattagtaac acaaatatct ttcaaaacct gtccacaact tttgtcataa 120 120 <210> 470 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 470_KRAS <400> 470 aaaaaataaa aactataatt actccttaat gtcagcttat tatattcaat ttaaacccac 60 ctataatggt gaatatcttc aaatgattta gtattattta tggcaaatac acaaagaaag 120 120 <210> 471 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 471_KRAS <400> 471 ctataatggt gaatatcttc aaatgattta gtattattta tggcaaatac acaaagaaag 60 ccctccccag tcctcatgta ctggtccctc attgcactgt actcctcttg acctgctgtg 120 120 <210> 472 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 472_KRAS <400> 472 ccctccccag tcctcatgta ctggtccctc attgcactgt actcctcttg acctgctgtg 60 tcgagaatat ccaagagaca ggtttctcca tcaattacta cttgcttcct gtaggaatcc 120 120 <210> 473 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 473_KRAS <400> 473 tcgagaatat ccaagagaca ggtttctcca tcaattacta cttgcttcct gtaggaatcc 60 tgagaaggga gaaacacagt ctggattatt acagtgcacc ttttacttca aaaaaggtgt 120 120 <210> 474 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 474_KRAS <400> 474 ctttatctgt atcaaagaat ggtcctgcac cagtaatatg catattaaaa caagatttac 60 ctctattgtt ggatcatatt cgtccacaaa atgattctga attagctgta tcgtcaaggc 120 120 <210> 475 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 475_KRAS <400> 475 ctctattgtt ggatcatatt cgtccacaaa atgattctga attagctgta tcgtcaaggc 60 actcttgcct acgccaccag ctccaactac cacaagttta tattcagtca ttttcagcag 120 120 <210> 476 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 476_KRAS <400> 476 actcttgcct acgccaccag ctccaactac cacaagttta tattcagtca ttttcagcag 60 gccttataat aaaaataatg aaaatgtgac tatattagaa catgtcacac ataaggttaa 120 120 <210> 477 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 477_KRAS <400> 477 gccttataat aaaaataatg aaaatgtgac tatattagaa catgtcacac ataaggttaa 60 tacactatca aatactccac cagtaccttt taatacaaac tcacctttat atgaaaaatt 120 120 <210> 478 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 478_TP53 <400> 478 gtgggaggct gtcagtgggg aacaagaagt ggagaatgtc agtctgagtc aggcccttct 60 gtcttgaaca tgagtttttt atggcgggag gtagactgac cctttttgga cttcaggtgg 120 120 <210> 479 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 479_TP53 <400> 479 tcagtctgag tcaggccctt ctgtcttgaa catgagtttt ttatggcggg aggtagactg 60 accctttttg gacttcaggt ggctgtagga gacagaagca gggaggagag atgacatcac 120 120 <210> 480 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 480_TP53 <400> 480 tgaggtcact cacctggagt gagccctgct cccccctggc tccttcccag cctgggcatc 60 cttgagttcc aaggcctcat tcagctctcg gaacatctcg aagcgctcac gcccacggat 120 120 <210> 481 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 481_TP53 <400> 481 ctggagtgag ccctgctccc ccctggctcc ttcccagcct gggcatcctt gagttccaag 60 gcctcattca gctctcggaa catctcgaag cgctcacgcc cacggatctg cagcaacaga 120 120 <210> 482 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 482_TP53 <400> 482 aggctaggct aagctatgat gttccttaga ttaggtgtat taaatccatt ttcaacttac 60 aatattttca acttacgacg agtttatcag gaagtaacac catcgtaagt caagtagcat 120 120 <210> 483 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 483_TP53 <400> 483 aatattttca acttacgacg agtttatcag gaagtaacac catcgtaagt caagtagcat 60 ctgtatcagg caaagtcata gaaccatttt catgctctct ttaacaattt tctttttgaa 120 120 <210> 484 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 484_TP53 <400> 484 ctgtatcagg caaagtcata gaaccatttt catgctctct ttaacaattt tctttttgaa 60 agctggtctg gtcctttaaa atatatatta tggtataagt tggtgttctg aagttagtta 120 120 <210> 485 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 485_TP53 <400> 485 agctggtctg gtcctttaaa atatatatta tggtataagt tggtgttctg aagttagtta 60 gctacaacca ggagccattg tctttgaggc atcactgccc cctgatggca aatgccccaa 120 120 <210> 486 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 486_TP53 <400> 486 tagactggaa actttccact tgataagagg tcccaagact tagtacctga agggtgaaat 60 attctccatc cagtggtttc ttctttggct ggggagagga gctggtgttg ttgggcagtg 120 120 <210> 487 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 487_TP53 <400> 487 ctgaagggtg aaatattctc catccagtgg tttcttcttt ggctggggag aggagctggt 60 gttgttgggc agtgctagga aagaggcaag gaaaggtgat aaaagtgaat ctgaggcata 120 120 <210> 488 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 488_TP53 <400> 488 gaatctgagg cataactgca cccttggtct cctccaccgc ttcttgtcct gcttgcttac 60 ctcgcttagt gctccctggg ggcagctcgt ggtgaggctc ccctttcttg cggagattct 120 120 <210> 489 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 489_TP53 <400> 489 ctcgcttagt gctccctggg ggcagctcgt ggtgaggctc ccctttcttg cggagattct 60 cttcctctgt gcgccggtct ctcccaggac aggcacaaac acgcacctca aagctgttcc 120 120 <210> 490 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 490_TP53 <400> 490 cttcctctgt gcgccggtct ctcccaggac aggcacaaac acgcacctca aagctgttcc 60 gtcccagtag attaccacta ctcaggatag gaaaagagaa gcaagaggca gtaaggaaat 120 120 <210> 491 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 491_TP53 <400> 491 gtcccagtag attaccacta ctcaggatag gaaaagagaa gcaagaggca gtaaggaaat 60 caggtcctac ctgtcccatt taaaaaacca ggctccatct actcccaacc acccttgtcc 120 120 <210> 492 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 492_TP53 <400> 492 ggctcctgac ctggagtctt ccagtgtgat gatggtgagg atgggcctcc ggttcatgcc 60 gcccatgcag gaactgttac acatgtagtt gtagtggatg gtggtacagt cagagccaac 120 120 <210> 493 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 493_TP53 <400> 493 ctggagtctt ccagtgtgat gatggtgagg atgggcctcc ggttcatgcc gcccatgcag 60 gaactgttac acatgtagtt gtagtggatg gtggtacagt cagagccaac ctaggagata 120 120 <210> 494 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 494_TP53 <400> 494 accagacctc aggcggctca tagggcacca ccacactatg tcgaaaagtg tttctgtcat 60 ccaaatactc cacacgcaaa tttccttcca ctcggataag atgctgagga ggggccagac 120 120 <210> 495 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 495_TP53 <400> 495 ctcaggcggc tcatagggca ccaccacact atgtcgaaaa gtgtttctgt catccaaata 60 ctccacacgc aaatttcctt ccactcggat aagatgctga ggaggggcca gacctaagag 120 120 <210> 496 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 496_TP53 <400> 496 tcagaggcct ggggaccctg ggcaaccagc cctgtcgtct ctccagcccc agctgctcac 60 catcgctatc tgagcagcgc tcatggtggg ggcagcgcct cacaacctcc gtcatgtgct 120 120 <210> 497 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 497_TP53 <400> 497 catcgctatc tgagcagcgc tcatggtggg ggcagcgcct cacaacctcc gtcatgtgct 60 gtgactgctt gtagatggcc atggcgcgga cgcgggtgcc gggcgggggt gtggaatcaa 120 120 <210> 498 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 498_TP53 <400> 498 gtgactgctt gtagatggcc atggcgcgga cgcgggtgcc gggcgggggt gtggaatcaa 60 cccacagctg cacagggcag gtcttggcca gttggcaaaa catcttgttg agggcagggg 120 120 <210> 499 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 499_TP53 <400> 499 cccacagctg cacagggcag gtcttggcca gttggcaaaa catcttgttg agggcagggg 60 agtactgtag gaagaggaag gagacagagt tgaaagtcag ggcacaagtg aacagataaa 120 120 <210> 500 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 500_TP53 <400> 500 agtactgtag gaagaggaag gagacagagt tgaaagtcag ggcacaagtg aacagataaa 60 gcaactggaa gacggcagca aagaaacaaa catgcgtaag cacctcctgc aacccactag 120 120 <210> 501 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 501_TP53 <400> 501 gcagggggat acggccaggc attgaagtct catggaagcc agcccctcag ggcaactgac 60 cgtgcaagtc acagacttgg ctgtcccaga atgcaagaag cccagacgga aaccgtagct 120 120 <210> 502 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 502_TP53 <400> 502 cgtgcaagtc acagacttgg ctgtcccaga atgcaagaag cccagacgga aaccgtagct 60 gccctggtag gttttctggg aagggacaga agatgacagg ggccaggagg gggctggtgc 120 120 <210> 503 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 503_TP53 <400> 503 gccctggtag gttttctggg aagggacaga agatgacagg ggccaggagg gggctggtgc 60 aggggccgcc ggtgtaggag ctgctggtgc aggggccacg gggggagcag cctctggcat 120 120 <210> 504 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 504_TP53 <400> 504 aggggccgcc ggtgtaggag ctgctggtgc aggggccacg gggggagcag cctctggcat 60 tctgggagct tcatctggac ctgggtcttc agtgaaccat tgttcaatat cgtccgggga 120 120 <210> 505 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 505_TP53 <400> 505 tctgggagct tcatctggac ctgggtcttc agtgaaccat tgttcaatat cgtccgggga 60 cagcatcaaa tcatccattg cttgggacgg caagggggac tgtagatggg tgaaaagagc 120 120 <210> 506 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 506_TP53 <400> 506 cagcatcaaa tcatccattg cttgggacgg caagggggac tgtagatggg tgaaaagagc 60 agtcagagga ccaggtcctc agccccccag ccccccagcc ctccaggtcc ccagccctcc 120 120 <210> 507 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 507_TP53 <400> 507 agccccccag ccctccaggt ccccagccct ccaggtcccc agcccaaccc ttgtccttac 60 cagaacgttg ttttcaggaa gtctgaaaga caagagcaga aagtcagtcc catggaattt 120 120 <210> 508 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 508_TP53 <400> 508 cagaacgttg ttttcaggaa gtctgaaaga caagagcaga aagtcagtcc catggaattt 60 tcgcttccca caggtctctg ctagggggct ggggttgggg tgggggtggt gggcctgccc 120 120 <210> 509 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 509_TP53 <400> 509 tcgcttccca caggtctctg ctagggggct ggggttgggg tgggggtggt gggcctgccc 60 ttccaatgga tccactcaca gtttccatag gtctgaaaat gtttcctgac tcagaggggg 120 120 <210> 510 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 510_TP53 <400> 510 ttccaatgga tccactcaca gtttccatag gtctgaaaat gtttcctgac tcagaggggg 60 ctcgacgcta ggatctgact gcggctcctc catggcagtg acccggaagg cagtctggct 120 120 <210> 511 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 511_TP53 <400> 511 ctcgacgcta ggatctgact gcggctcctc catggcagtg acccggaagg cagtctggct 60 gctgcaagag gaaaagtggg gatccagcat gagacacttc caaccctggg tcacctgggc 120 120 <210> 512 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 512_TP53 <400> 512 gctgcaagag gaaaagtggg gatccagcat gagacacttc caaccctggg tcacctgggc 60 ctgcagagaa ggaaccccct cccccaacac catgccagtg tctgagacag ctcggcttcc 120 120 <210> 513 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 513_ERBB2 <400> 513 tcttttttct tctagtcgca attgaagtac cacctcccga gggtgattgc ttccccatgc 60 ggggtagaac ctttgctgtc ctgttcacca ctctacctcc agcacagaat ttggcttatg 120 120 <210> 514 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 514_ERBB2 <400> 514 tcgcaattga agtaccacct cccgagggtg attgcttccc catgcggggt agaacctttg 60 ctgtcctgtt caccactcta cctccagcac agaatttggc ttatggtagg cgctaactgc 120 120 <210> 515 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 515_ERBB2 <400> 515 ccccaaaata gcaagaccaa ccccatctct tttcctttct cttccccctc ctcagcctac 60 tcaatgtgaa gatgatgagg atgaaaacct ttgtgatgat ccacttccac ttaatgaatg 120 120 <210> 516 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 516_ERBB2 <400> 516 cctactcaat gtgaagatga tgaggatgaa aacctttgtg atgatccact tccacttaat 60 gaatggtaaa tatgtttttt cttacttatg attttcttag tagcattttc ttttctctag 120 120 <210> 517 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 517_ERBB2 <400> 517 ctataccaaa tccgaaaata ttgtgaccag gaaccattct gtccaactct tctatttcag 60 gtggcaaagc aaagctatat tcaagaccac atgcaaagct actccctgag caaagagtca 120 120 <210> 518 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 518_ERBB2 <400> 518 gtggcaaagc aaagctatat tcaagaccac atgcaaagct actccctgag caaagagtca 60 cagataaaac gggggcacca gtagaatggc caggacaaac gcagtgcagc acagagactc 120 120 <210> 519 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 519_ERBB2 <400> 519 cagataaaac gggggcacca gtagaatggc caggacaaac gcagtgcagc acagagactc 60 agaccctggc agccatgcct gcgcaggcag tgatgagagt gacatgtact gttgtggaca 120 120 <210> 520 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 520_ERBB2 <400> 520 agaccctggc agccatgcct gcgcaggcag tgatgagagt gacatgtact gttgtggaca 60 tgcacaaaag tgaggtgagt cgcaggacag aagagtgctt tttgtttcag cagagcagcc 120 120 <210> 521 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 521_ERBB2 <400> 521 tgcacaaaag tgaggtgagt cgcaggacag aagagtgctt tttgtttcag cagagcagcc 60 tggggagaga taaaagctac tcctggggcc tgggcctgca ttcctgagat gtgggtaaga 120 120 <210> 522 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 522_ERBB2 <400> 522 aaaaaaagtc ctttcgatgt gactgtctcc tcccaaattt gtagaccctc ttaagatcat 60 gcttttcaga tacttcaaag attccagaag atatgccccg ggggtcctgg aagccacaag 120 120 <210> 523 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 523_ERBB2 <400> 523 atacttcaaa gattccagaa gatatgcccc gggggtcctg gaagccacaa ggtaaacaca 60 acacatcccc ctccttgact atcaatttta ctagaggatg tggtgggaaa accattattt 120 120 <210> 524 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 524_ERBB2 <400> 524 cagccgggtc cagccggagc catggggccg gagccgcagt gagcaccatg gagctggcgg 60 ccttgtgccg ctgggggctc ctcctcgccc tcttgccccc cggagccgcg agcacccaag 120 120 <210> 525 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 525_ERBB2 <400> 525 atggagctgg cggccttgtg ccgctggggg ctcctcctcg ccctcttgcc ccccggagcc 60 gcgagcaccc aaggtgggtc tggtgtgggg aggggacgga gcagcggcgg gaccctgccc 120 120 <210> 526 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 526_ERBB2 <400> 526 ggccaggtct gagaaggtcc cccgccagtg tcctctgacc catctgctct ctcctgccag 60 tgtgcaccgg cacagacatg aagctgcggc tccctgccag tcccgagacc cacctggaca 120 120 <210> 527 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 527_ERBB2 <400> 527 tgtgcaccgg cacagacatg aagctgcggc tccctgccag tcccgagacc cacctggaca 60 tgctccgcca cctctaccag ggctgccagg tggtgcaggg aaacctggaa ctcacctacc 120 120 <210> 528 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 528_ERBB2 <400> 528 tgctccgcca cctctaccag ggctgccagg tggtgcaggg aaacctggaa ctcacctacc 60 tgcccaccaa tgccagcctg tccttcctgc aggtgaggcc cgtgggcaac ccagccaggc 120 120 <210> 529 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 529_ERBB2 <400> 529 tgcccaccaa tgccagcctg tccttcctgc aggtgaggcc cgtgggcaac ccagccaggc 60 cctgcctcca gctgggctga gccctctgtt tacaggtggg tggcagaaga aggtgccctg 120 120 <210> 530 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 530_ERBB2 <400> 530 cctgcctcca gctgggctga gccctctgtt tacaggtggg tggcagaaga aggtgccctg 60 cccttctgtt tcctctcttg ttgtggtttc tcaaccagga agtcctttct aacatctaac 120 120 <210> 531 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 531_ERBB2 <400> 531 gggaggccct ggggggtggc agtgttccta tttcagcccc actctgcttc cccctcccag 60 gatatccagg aggtgcaggg ctacgtgctc atcgctcaca accaagtgag gcaggtccca 120 120 <210> 532 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 532_ERBB2 <400> 532 gatatccagg aggtgcaggg ctacgtgctc atcgctcaca accaagtgag gcaggtccca 60 ctgcagaggc tgcggattgt gcgaggcacc cagctctttg aggacaacta tgccctggcc 120 120 <210> 533 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 533_ERBB2 <400> 533 ctgcagaggc tgcggattgt gcgaggcacc cagctctttg aggacaacta tgccctggcc 60 gtgctagaca atggagaccc gctgaacaat accacccctg tcacaggggc ctccccagga 120 120 <210> 534 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 534_ERBB2 <400> 534 gtgctagaca atggagaccc gctgaacaat accacccctg tcacaggggc ctccccagga 60 ggcctgcggg agctgcagct tcgaagcctc acaggtggcc ttcaccgtca ttgaaacctt 120 120 <210> 535 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 535_ERBB2 <400> 535 ggcctgcggg agctgcagct tcgaagcctc acaggtggcc ttcaccgtca ttgaaacctt 60 ctcttggtta ttcagagctg accagggcca ctgctaacca gggggaggct ttgtgtgcat 120 120 <210> 536 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 536_ERBB2 <400> 536 caagggaagc agaaggtgac agaaggggaa agggtcctct gatcattgct caccccacag 60 agatcttgaa aggaggggtc ttgatccagc ggaaccccca gctctgctac caggacacga 120 120 <210> 537 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 537_ERBB2 <400> 537 agatcttgaa aggaggggtc ttgatccagc ggaaccccca gctctgctac caggacacga 60 ttttgtggaa ggacatcttc cacaagaaca accagctggc tctcacactg atagacacca 120 120 <210> 538 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 538_ERBB2 <400> 538 ttttgtggaa ggacatcttc cacaagaaca accagctggc tctcacactg atagacacca 60 accgctctcg ggcctgtaag ccatgcccct ccctgctgcc tcttctctca gacagcctga 120 120 <210> 539 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 539_ERBB2 <400> 539 accgctctcg ggcctgtaag ccatgcccct ccctgctgcc tcttctctca gacagcctga 60 ccccagccgc aaactcccaa cttacaaccc agtgcctgcc cgccactgcc ccagccgcct 120 120 <210> 540 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 540_ERBB2 <400> 540 ctctcgctgt tagacatctc tctcactgcc tgtctctggt tctgtcctca ggccacccct 60 gttctccgat gtgtaagggc tcccgctgct ggggagagag ttctgaggat tgtcagagcc 120 120 <210> 541 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 541_ERBB2 <400> 541 gccacccctg ttctccgatg tgtaagggct cccgctgctg gggagagagt tctgaggatt 60 gtcagagccg tgagtctcag ggaggcctgg agtcagggaa ggggagggct ggggccgggt 120 120 <210> 542 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 542_ERBB2 <400> 542 acagtgacgc gcactgtctg tgccggtggc tgtgcccgct gcaaggggcc actgcccact 60 gactgctgcc atgagcagtg tgctgccggc tgcacgggcc ccaagcactc tgactgcctg 120 120 <210> 543 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 543_ERBB2 <400> 543 tgacgcgcac tgtctgtgcc ggtggctgtg cccgctgcaa ggggccactg cccactgact 60 gctgccatga gcagtgtgct gccggctgca cgggccccaa gcactctgac tgcctggtat 120 120 <210> 544 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 544_ERBB2 <400> 544 attgcccctg gcacaccagg gcaaaacagc acagtgaaag ccagccacct gtccccccag 60 gcctgcctcc acttcaacca cagtggcatc tgtgagctgc actgcccagc cctggtcacc 120 120 <210> 545 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 545_ERBB2 <400> 545 gcctgcctcc acttcaacca cagtggcatc tgtgagctgc actgcccagc cctggtcacc 60 tacaacacag acacgtttga gtccatgccc aatcccgagg gccggtatac attcggcgcc 120 120 <210> 546 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 546_ERBB2 <400> 546 tacaacacag acacgtttga gtccatgccc aatcccgagg gccggtatac attcggcgcc 60 agctgtgtga ctgcctgtcc ctgtgagtgc cagggagaaa cacagttttc tcattttggt 120 120 <210> 547 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 547_ERBB2 <400> 547 agctgtgtga ctgcctgtcc ctgtgagtgc cagggagaaa cacagttttc tcattttggt 60 ggggaggttt gtttctgtaa atgggagcat atggggagca ctgtctgcat cttgctttga 120 120 <210> 548 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 548_ERBB2 <400> 548 ctgctcatgg tggtgcacga agggccaggg tatgtggcta catgttcctg atctccttag 60 acaactacct ttctacggac gtgggatcct gcaccctcgt ctgccccctg cacaaccaag 120 120 <210> 549 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 549_ERBB2 <400> 549 acaactacct ttctacggac gtgggatcct gcaccctcgt ctgccccctg cacaaccaag 60 aggtgacagc agaggatgga acacagcggt gtgagaagtg cagcaagccc tgtgcccgag 120 120 <210> 550 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 550_ERBB2 <400> 550 aggtgacagc agaggatgga acacagcggt gtgagaagtg cagcaagccc tgtgcccgag 60 gtacccactc actgcccccg aggccagctg cagttcctgt ccctctgcgc atgcagcctg 120 120 <210> 551 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 551_ERBB2 <400> 551 tgacctgtcc cggtatgaag gctgagacgg ccccttcccc acccaccccc acctcctcag 60 tgtgctatgg tctgggcatg gagcacttgc gagaggtgag ggcagttacc agtgccaata 120 120 <210> 552 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 552_ERBB2 <400> 552 tgtgctatgg tctgggcatg gagcacttgc gagaggtgag ggcagttacc agtgccaata 60 tccaggagtt tgctggctgc aagaagatct ttgggagcct ggcatttctg ccggagagct 120 120 <210> 553 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 553_ERBB2 <400> 553 tccaggagtt tgctggctgc aagaagatct ttgggagcct ggcatttctg ccggagagct 60 ttgatgggta agagtgggca cgatgacctg agacagtgtc agggcagaca gagtcctgag 120 120 <210> 554 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 554_ERBB2 <400> 554 ttgatgggta agagtgggca cgatgacctg agacagtgtc agggcagaca gagtcctgag 60 gatccagatg tggcagcatc tcttggggat ggcaggagac agaagtgggg ggatcaagaa 120 120 <210> 555 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 555_ERBB2 <400> 555 tccaccctgt tcctggccct gctgactcct ctcctgaccc ctccagggac ccagcctcca 60 acactgcccc gctccagcca gagcagctcc aagtgtttga gactctggaa gagatcacag 120 120 <210> 556 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 556_ERBB2 <400> 556 ggacccagcc tccaacactg ccccgctcca gccagagcag ctccaagtgt ttgagactct 60 ggaagagatc acaggtgggc tctgtctctg catcctgttc tgcaggggct gggagtcctt 120 120 <210> 557 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 557_ERBB2 <400> 557 actcctttaa tctcaccctc tgcctgcagg ttacctatac atctcagcat ggccggacag 60 cctgcctgac ctcagcgtct tccagaacct gcaagtaatc cggggacgaa ttctgcacaa 120 120 <210> 558 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 558_ERBB2 <400> 558 gttacctata catctcagca tggccggaca gcctgcctga cctcagcgtc ttccagaacc 60 tgcaagtaat ccggggacga attctgcaca agtgagcact gagaaagagg gggcctgatg 120 120 <210> 559 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 559_ERBB2 <400> 559 agaatagcct ttgctgaccg ggaaggggtc cgtggtaagg tgcccacctt tctcccatag 60 tggcgcctac tcgctgaccc tgcaagggct gggcatcagc tggctggggc tgcgctcact 120 120 <210> 560 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 560_ERBB2 <400> 560 tggcgcctac tcgctgaccc tgcaagggct gggcatcagc tggctggggc tgcgctcact 60 gagggaactg ggcagtggac tggccctcat ccaccataac acccacctct gcttcgtgca 120 120 <210> 561 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 561_ERBB2 <400> 561 gagggaactg ggcagtggac tggccctcat ccaccataac acccacctct gcttcgtgca 60 cacggtgccc tgggaccagc tctttcggaa cccgcaccaa gctctgctcc acactgccaa 120 120 <210> 562 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 562_ERBB2 <400> 562 cacggtgccc tgggaccagc tctttcggaa cccgcaccaa gctctgctcc acactgccaa 60 ccggccagag gacgagtgtg gtaagacagg gagcccagtg tgcgcactcc ccatctgcca 120 120 <210> 563 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 563_ERBB2 <400> 563 ccggccagag gacgagtgtg gtaagacagg gagcccagtg tgcgcactcc ccatctgcca 60 gcacacagca gtgcccaggg ggccctggca gcagcgttct tggacttgtg cagactgccc 120 120 <210> 564 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 564_ERBB2 <400> 564 ttcacttgga cctggggcct cccctaaaag tcccctgcgg tcccttcctc ctcactgcag 60 tgggcgaggg cctggcctgc caccagctgt gcgcccgagg gcactgctgg ggtccagggc 120 120 <210> 565 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 565_ERBB2 <400> 565 tgggcgaggg cctggcctgc caccagctgt gcgcccgagg gcactgctgg ggtccagggc 60 ccacccagtg tgtcaactgc agccagttcc ttcggggcca ggagtgcgtg gaggaatgcc 120 120 <210> 566 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 566_ERBB2 <400> 566 ccacccagtg tgtcaactgc agccagttcc ttcggggcca ggagtgcgtg gaggaatgcc 60 gagtactgca ggggtatgag gggcggagga gagggtggct ggaggggtgc atggggctcc 120 120 <210> 567 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 567_ERBB2 <400> 567 gagtactgca ggggtatgag gggcggagga gagggtggct ggaggggtgc atggggctcc 60 tctcagaccc cctcaccact gtcccttctc tcaggctccc cagggagtat gtgaatgcca 120 120 <210> 568 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 568_ERBB2 <400> 568 gaccccctca ccactgtccc ttctctcagg ctccccaggg agtatgtgaa tgccaggcac 60 tgtttgccgt gccaccctga gtgtcagccc cagaatggct cagtgacctg ttttggaccg 120 120 <210> 569 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 569_ERBB2 <400> 569 gctccccagg gagtatgtga atgccaggca ctgtttgccg tgccaccctg agtgtcagcc 60 ccagaatggc tcagtgacct gttttggacc ggtgagctgc tggcgggctc agagctgggt 120 120 <210> 570 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 570_ERBB2 <400> 570 atcctactgc cctgggggtg tcagtgccag ccccccacaa atcttttctg ccccccccag 60 gaggctgacc agtgtgtggc ctgtgcccac tataaggacc ctcccttctg cgtggcccgc 120 120 <210> 571 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 571_ERBB2 <400> 571 gaggctgacc agtgtgtggc ctgtgcccac tataaggacc ctcccttctg cgtggcccgc 60 tgccccagcg gtgtgaaacc tgacctctcc tacatgccca tctggaagtt tccagatgag 120 120 <210> 572 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 572_ERBB2 <400> 572 tgccccagcg gtgtgaaacc tgacctctcc tacatgccca tctggaagtt tccagatgag 60 gagggcgcat gccagccttg ccccatcaac tgcacccact cgtgagtcca acggtctttt 120 120 <210> 573 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 573_ERBB2 <400> 573 gagggcgcat gccagccttg ccccatcaac tgcacccact cgtgagtcca acggtctttt 60 ctgcagaaag gaggactttc ctttcagggg tctttctggg gctcttacta taaaagggga 120 120 <210> 574 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 574_ERBB2 <400> 574 gttgtgaggc tggaaaggtg gttcccaaga gggtggttcc cagaattgtt gatgagactg 60 tttctcctgc agctgtgtgg acctggatga caagggctgc cccgccgagc agagagccag 120 120 <210> 575 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 575_ERBB2 <400> 575 ctgtgtggac ctggatgaca agggctgccc cgccgagcag agagccaggt tggcctggac 60 cccaggatgt acccttcatt gcccttcact cccccactgg atgctgggtg gtcactgctg 120 120 <210> 576 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 576_ERBB2 <400> 576 ccctttgtcc ctcccacccc aaactagccc tcaatccctg accctggctt ccgcccccag 60 ccctctgacg tccatcatct ctgcggtggt tggcattctg ctggtcgtgg tcttgggggt 120 120 <210> 577 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 577_ERBB2 <400> 577 ccctctgacg tccatcatct ctgcggtggt tggcattctg ctggtcgtgg tcttgggggt 60 ggtctttggg atcctcatca agcgacggca gcagaagatc cggaagtaca cgatgcggag 120 120 <210> 578 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 578_ERBB2 <400> 578 ggtctttggg atcctcatca agcgacggca gcagaagatc cggaagtaca cgatgcggag 60 actgctgcag gaaacggagg tgaggcgggg tgaagtcctc ccagcccgcg tggggtctgc 120 120 <210> 579 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 579_ERBB2 <400> 579 actgctgcag gaaacggagg tgaggcgggg tgaagtcctc ccagcccgcg tggggtctgc 60 accggccccc ggcactgacc caccaccccc tcaccccagc tggtggagcc gctgacacct 120 120 <210> 580 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 580_ERBB2 <400> 580 cccagcccgc gtggggtctg caccggcccc cggcactgac ccaccacccc ctcaccccag 60 ctggtggagc cgctgacacc tagcggagcg atgcccaacc aggcgcagat gcggatcctg 120 120 <210> 581 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 581_ERBB2 <400> 581 ctggtggagc cgctgacacc tagcggagcg atgcccaacc aggcgcagat gcggatcctg 60 aaagagacgg agctgaggaa ggtgaaggtg cttggatctg gcgcttttgg cacagtctac 120 120 <210> 582 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 582_ERBB2 <400> 582 aaagagacgg agctgaggaa ggtgaaggtg cttggatctg gcgcttttgg cacagtctac 60 aaggtcaggg ccaggtcctg gggtgggcgg ccccagagga tgggggcggt gcctggaggg 120 120 <210> 583 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 583_ERBB2 <400> 583 aaggtcaggg ccaggtcctg gggtgggcgg ccccagagga tgggggcggt gcctggaggg 60 gtgtggtcgg cagttctgat gggaggggca agagctggag gcagtgtttg ggggagggca 120 120 <210> 584 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 584_ERBB2 <400> 584 tatcctcctc tttctgccca gggcatctgg atccctgatg gggagaatgt gaaaattcca 60 gtggccatca aagtgttgag ggaaaacaca tcccccaaag ccaacaaaga aatcttagac 120 120 <210> 585 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 585_ERBB2 <400> 585 ggcatctgga tccctgatgg ggagaatgtg aaaattccag tggccatcaa agtgttgagg 60 gaaaacacat cccccaaagc caacaaagaa atcttagacg taagcccctc caccctctcc 120 120 <210> 586 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 586_ERBB2 <400> 586 ctgtgtggtg tttgggggtg tgtggtctcc cataccctct cagcgtaccc ttgtccccag 60 gaagcatacg tgatggctgg tgtgggctcc ccatatgtct cccgccttct gggcatctgc 120 120 <210> 587 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 587_ERBB2 <400> 587 gaagcatacg tgatggctgg tgtgggctcc ccatatgtct cccgccttct gggcatctgc 60 ctgacatcca cggtgcagct ggtgacacag cttatgccct atggctgcct cttagaccat 120 120 <210> 588 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 588_ERBB2 <400> 588 ctgacatcca cggtgcagct ggtgacacag cttatgccct atggctgcct cttagaccat 60 gtccgggaaa accgcggacg cctgggctcc caggacctgc tgaactggtg tatgcagatt 120 120 <210> 589 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 589_ERBB2 <400> 589 gtccgggaaa accgcggacg cctgggctcc caggacctgc tgaactggtg tatgcagatt 60 gccaaggtat gcacctgggc tctttgcagg tctctccgga gcaaacccct atgtccacaa 120 120 <210> 590 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 590_ERBB2 <400> 590 gccaaggtat gcacctgggc tctttgcagg tctctccgga gcaaacccct atgtccacaa 60 ggggctagga tggggactct tgctgggcat gtggccaggc ccaggccctc ccagaaggtc 120 120 <210> 591 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 591_ERBB2 <400> 591 tgggcatgtg gccaggccca ggccctccca gaaggtctac atgggtgctt cccattccag 60 gggatgagct acctggagga tgtgcggctc gtacacaggg acttggccgc tcggaacgtg 120 120 <210> 592 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 592_ERBB2 <400> 592 gggatgagct acctggagga tgtgcggctc gtacacaggg acttggccgc tcggaacgtg 60 ctggtcaaga gtcccaacca tgtcaaaatt acagacttcg ggctggctcg gctgctggac 120 120 <210> 593 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 593_ERBB2 <400> 593 ctggtcaaga gtcccaacca tgtcaaaatt acagacttcg ggctggctcg gctgctggac 60 attgacgaga cagagtacca tgcagatggg ggcaaggtta ggtgaaggac caaggagcag 120 120 <210> 594 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 594_ERBB2 <400> 594 attgacgaga cagagtacca tgcagatggg ggcaaggtta ggtgaaggac caaggagcag 60 aggaggctgg gtggagtggt gtctagccca tgggagaact ctgagtggcc acctccccac 120 120 <210> 595 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 595_ERBB2 <400> 595 ccccacaaca cacagttgga ggacttcctc ttctgccctc ccaggtgccc atcaagtgga 60 tggcgctgga gtccattctc cgccggcggt tcacccacca gagtgatgtg tggagttatg 120 120 <210> 596 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 596_ERBB2 <400> 596 gtgcccatca agtggatggc gctggagtcc attctccgcc ggcggttcac ccaccagagt 60 gatgtgtgga gttatggtgt gtgatggggg gtgttgggag gggtgggtga ggagccatgg 120 120 <210> 597 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 597_ERBB2 <400> 597 tggctcagta cactaaagct ccctctggcc ctcccactcc tgaccctgtc tctgccttag 60 gtgtgactgt gtgggagctg atgacttttg gggccaaacc ttacgatggg atcccagccc 120 120 <210> 598 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 598_ERBB2 <400> 598 gtgtgactgt gtgggagctg atgacttttg gggccaaacc ttacgatggg atcccagccc 60 gggagatccc tgacctgctg gaaaaggggg agcggctgcc ccagcccccc atctgcacca 120 120 <210> 599 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 599_ERBB2 <400> 599 gggagatccc tgacctgctg gaaaaggggg agcggctgcc ccagcccccc atctgcacca 60 ttgatgtcta catgatcatg gtcaaatgtg cgtggctgag ctgtgctggc tgcctggagg 120 120 <210> 600 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 600_ERBB2 <400> 600 ttgatgtcta catgatcatg gtcaaatgtg cgtggctgag ctgtgctggc tgcctggagg 60 agggtgggag gtcctgggtg gaggagccca caaggggcat gaaaggggac caggatgtat 120 120 <210> 601 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 601_ERBB2 <400> 601 gctgacctcc ctcctgcccc aggttggatg attgactctg aatgtcggcc aagattccgg 60 gagttggtgt ctgaattctc ccgcatggcc agggaccccc agcgctttgt ggtcatccag 120 120 <210> 602 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 602_ERBB2 <400> 602 gttggatgat tgactctgaa tgtcggccaa gattccggga gttggtgtct gaattctccc 60 gcatggccag ggacccccag cgctttgtgg tcatccaggt actgggcctc tgtgccccat 120 120 <210> 603 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 603_ERBB2 <400> 603 acggaaggct gcatgctggg ctggggaggg gccaccatcc tgcctctcct tcctccacag 60 aatgaggact tgggcccagc cagtcccttg gacagcacct tctaccgctc actgctggag 120 120 <210> 604 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 604_ERBB2 <400> 604 aatgaggact tgggcccagc cagtcccttg gacagcacct tctaccgctc actgctggag 60 gacgatgaca tgggggacct ggtggatgct gaggagtatc tggtacccca gcagggcttc 120 120 <210> 605 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 605_ERBB2 <400> 605 gacgatgaca tgggggacct ggtggatgct gaggagtatc tggtacccca gcagggcttc 60 ttctgtccag accctgcccc gggcgctggg ggcatggtcc accacaggca ccgcagctca 120 120 <210> 606 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 606_ERBB2 <400> 606 ttctgtccag accctgcccc gggcgctggg ggcatggtcc accacaggca ccgcagctca 60 tctaccaggg tcagtgccct cggtcacact gtgtggctgt ctgcttacct cccccaaccc 120 120 <210> 607 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 607_ERBB2 <400> 607 tctaccaggg tcagtgccct cggtcacact gtgtggctgt ctgcttacct cccccaaccc 60 cggtggacta gggtcccttt ctctgatgtt ccctcaactg tcacctctca aggaaacccc 120 120 <210> 608 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 608_ERBB2 <400> 608 tggagtcccc atcccagatc cgtgagtgac ccccatcatg actttctttc ttgtccccag 60 agtggcggtg gggacctgac actagggctg gagccctctg aagaggaggc ccccaggtct 120 120 <210> 609 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 609_ERBB2 <400> 609 agtggcggtg gggacctgac actagggctg gagccctctg aagaggaggc ccccaggtct 60 ccactggcac cctccgaagg ggctggctcc gatgtatttg atggtgacct gggaatgggg 120 120 <210> 610 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 610_ERBB2 <400> 610 ccactggcac cctccgaagg ggctggctcc gatgtatttg atggtgacct gggaatgggg 60 gcagccaagg ggctgcaaag cctccccaca catgacccca gccctctaca gcggtacagt 120 120 <210> 611 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 611_ERBB2 <400> 611 gcagccaagg ggctgcaaag cctccccaca catgacccca gccctctaca gcggtacagt 60 gaggacccca cagtacccct gccctctgag actgatggct acgttgcccc cctgacctgc 120 120 <210> 612 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 612_ERBB2 <400> 612 gaggacccca cagtacccct gccctctgag actgatggct acgttgcccc cctgacctgc 60 agcccccagc ctggtatgga gtccagtcta agcagagaga ctgatgggca ggggaggtgg 120 120 <210> 613 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 613_ERBB2 <400> 613 agcccccagc ctggtatgga gtccagtcta agcagagaga ctgatgggca ggggaggtgg 60 gaccttcagc ccagggtcca ctgtgggggc agagggagtg gcagagacac cggggttcct 120 120 <210> 614 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 614_ERBB2 <400> 614 ggagtggcag agacaccggg gttccttccc ctaatgggtc accttctctt gacctttcag 60 aatatgtgaa ccagccagat gttcggcccc agcccccttc gccccgagag ggccctctgc 120 120 <210> 615 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 615_ERBB2 <400> 615 aatatgtgaa ccagccagat gttcggcccc agcccccttc gccccgagag ggccctctgc 60 ctgctgcccg acctgctggt gccactctgg aaaggcccaa gactctctcc ccagggaaga 120 120 <210> 616 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 616_ERBB2 <400> 616 ctgctgcccg acctgctggt gccactctgg aaaggcccaa gactctctcc ccagggaaga 60 atggggtcgt caaagacgtt tttgcctttg ggggtgccgt ggagaacccc gagtacttga 120 120 <210> 617 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 617_ERBB2 <400> 617 atggggtcgt caaagacgtt tttgcctttg ggggtgccgt ggagaacccc gagtacttga 60 caccccaggg aggagctgcc cctcagcccc accctcctcc tgccttcagc ccagccttcg 120 120 <210> 618 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 618_ERBB2 <400> 618 caccccaggg aggagctgcc cctcagcccc accctcctcc tgccttcagc ccagccttcg 60 acaacctcta ttactgggac caggacccac cagagcgggg ggctccaccc agcaccttca 120 120 <210> 619 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 619_ERBB2 <400> 619 acaacctcta ttactgggac caggacccac cagagcgggg ggctccaccc agcaccttca 60 aagggacacc tacggcagag aacccagagt acctgggtct ggacgtgcca gtgtgaacca 120 120 <210> 620 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 620_ERBB2 <400> 620 aagggacacc tacggcagag aacccagagt acctgggtct ggacgtgcca gtgtgaacca 60 gaaggccaag tccgcagaag ccctgatgtg tcctcaggga gcagggaagg cctgacttct 120 120 <210> 621 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 621_ERBB2 <400> 621 gaaggccaag tccgcagaag ccctgatgtg tcctcaggga gcagggaagg cctgacttct 60 gctggcatca agaggtggga gggccctccg accacttcca ggggaacctg ccatgccagg 120 120 <210> 622 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 622_ERBB2 <400> 622 gctggcatca agaggtggga gggccctccg accacttcca ggggaacctg ccatgccagg 60 aacctgtcct aaggaacctt ccttcctgct tgagttccca gatggctgga aggggtccag 120 120 <210> 623 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 623_ERBB2 <400> 623 aacctgtcct aaggaacctt ccttcctgct tgagttccca gatggctgga aggggtccag 60 cctcgttgga agaggaacag cactggggag tctttgtgga ttctgaggcc ctgcccaatg 120 120 <210> 624 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 624_ERBB2 <400> 624 cctcgttgga agaggaacag cactggggag tctttgtgga ttctgaggcc ctgcccaatg 60 agactctagg gtccagtgga tgccacagcc cagcttggcc ctttccttcc agatcctggg 120 120 <210> 625 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 625_ERBB2 <400> 625 agactctagg gtccagtgga tgccacagcc cagcttggcc ctttccttcc agatcctggg 60 tactgaaagc cttagggaag ctggcctgag aggggaagcg gccctaaggg agtgtctaag 120 120 <210> 626 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 626_ERBB2 <400> 626 tactgaaagc cttagggaag ctggcctgag aggggaagcg gccctaaggg agtgtctaag 60 aacaaaagcg acccattcag agactgtccc tgaaacctag tactgccccc catgaggaag 120 120 <210> 627 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 627_ERBB2 <400> 627 aacaaaagcg acccattcag agactgtccc tgaaacctag tactgccccc catgaggaag 60 gaacagcaat ggtgtcagta tccaggcttt gtacagagtg cttttctgtt tagtttttac 120 120 <210> 628 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 628_ERBB2 <400> 628 gaacagcaat ggtgtcagta tccaggcttt gtacagagtg cttttctgtt tagtttttac 60 tttttttgtt ttgttttttt aaagatgaaa taaagaccca gggggagaat gggtgttgta 120 120 <210> 629 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 629_ERBB2 <400> 629 tttttttgtt ttgttttttt aaagatgaaa taaagaccca gggggagaat gggtgttgta 60 tggggaggca agtgtggggg gtccttctcc acacccactt tgtccatttg caaatatatt 120 120 <210> 630 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 630_ERBB2 <400> 630 tggggaggca agtgtggggg gtccttctcc acacccactt tgtccatttg caaatatatt 60 ttggaaaaca gctaggcacc ggcctatgtc tgggggtggc tctgtgccat cccttcctgc 120 120 <210> 631 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 631_ERBB2 <400> 631 ttggaaaaca gctaggcacc ggcctatgtc tgggggtggc tctgtgccat cccttcctgc 60 tcaccttaca ctcaattcct cttttcctgg agggagtggc tgggaatctt cagaaagctt 120 120 <210> 632 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 632_SMAD4 <400> 632 agtcagatct acttcgtaaa atgtgttctg atgtgtgtct tttttttttt tcttttttag 60 gttatcctga atacatgtct aacaattttc cttgcaacgt tagctgttgt ttttcactgt 120 120 <210> 633 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 633_SMAD4 <400> 633 gttatcctga atacatgtct aacaattttc cttgcaacgt tagctgttgt ttttcactgt 60 ttccaaagga tcaaaattgc ttcagaaatt ggagacatat ttgatttaaa aggaaaaact 120 120 <210> 634 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 634_SMAD4 <400> 634 ttccaaagga tcaaaattgc ttcagaaatt ggagacatat ttgatttaaa aggaaaaact 60 tgaacaaatg gacaatatgt ctattacgaa tacaccaaca agtaatgatg cctgtctgag 120 120 <210> 635 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 635_SMAD4 <400> 635 tgaacaaatg gacaatatgt ctattacgaa tacaccaaca agtaatgatg cctgtctgag 60 cattgtgcat agtttgatgt gccatagaca aggtggagag agtgaaacat ttgcaaaaag 120 120 <210> 636 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 636_SMAD4 <400> 636 cattgtgcat agtttgatgt gccatagaca aggtggagag agtgaaacat ttgcaaaaag 60 agcaattgaa agtttggtaa agaagctgaa ggagaaaaaa gatgaattgg attctttaat 120 120 <210> 637 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 637_SMAD4 <400> 637 agcaattgaa agtttggtaa agaagctgaa ggagaaaaaa gatgaattgg attctttaat 60 aacagctata actacaaatg gagctcatcc tagtaaatgt gttaccatac agagaacatt 120 120 <210> 638 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 638_SMAD4 <400> 638 aacagctata actacaaatg gagctcatcc tagtaaatgt gttaccatac agagaacatt 60 ggatgggagg cttcaggtta gtcttataag agtttttcta taccctctat ggtggcagat 120 120 <210> 639 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 639_SMAD4 <400> 639 ggatgggagg cttcaggtta gtcttataag agtttttcta taccctctat ggtggcagat 60 ttaaaaactt gctacgtttc ctttcaagct actacagggt aatttaattt gtgctccatc 120 120 <210> 640 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 640_SMAD4 <400> 640 aatatataaa agtgtcttgc ataatgtgac acatgaataa atggtcgttt atttttctag 60 gtggctggtc ggaaaggatt tcctcatgtg atctatgccc gtctctggag gtggcctgat 120 120 <210> 641 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 641_SMAD4 <400> 641 gtggctggtc ggaaaggatt tcctcatgtg atctatgccc gtctctggag gtggcctgat 60 cttcacaaaa atgaactaaa acatgttaaa tattgtcagt atgcgtttga cttaaaatgt 120 120 <210> 642 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 642_SMAD4 <400> 642 cttcacaaaa atgaactaaa acatgttaaa tattgtcagt atgcgtttga cttaaaatgt 60 gatagtgtct gtgtgaatcc atatcactac gaacgagttg tatcacctgg aattggtaag 120 120 <210> 643 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 643_SMAD4 <400> 643 gatagtgtct gtgtgaatcc atatcactac gaacgagttg tatcacctgg aattggtaag 60 tagactttgc tttcatccta agaaacataa agggaaaagg atctcaatag tgtttcaatt 120 120 <210> 644 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 644_SMAD4 <400> 644 ggtttaaatt tacattctct gtttttaaat ggaaaatact ttcattgtaa tgattaatgt 60 ttcatttgtt ttccccttta aacaattaag atctctcagg attaacactg cagagtaatg 120 120 <210> 645 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 645_SMAD4 <400> 645 atctctcagg attaacactg cagagtaatg gtaggtaatc tgtttcttac tactttctct 60 ttgttttgtc ctatcctctc tgtttttttg ttgacctaga attagtttgt gtgagcggca 120 120 <210> 646 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 646_SMAD4 <400> 646 tttttttttc tgggaataga agcttataaa aatttaaaat atgtttaatt ttctatatag 60 ctccatcaag tatgatggtg aaggatgaat atgtgcatga ctttgaggga cagccatcgt 120 120 <210> 647 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 647 <400> 647 ctccatcaag tatgatggtg aaggatgaat atgtgcatga ctttgaggga cagccatcgt 60 tgtccactga aggacattca attcaaacca tccagcatcc accaagtaat cgtgcatcga 120 120 <210> 648 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 648_SMAD4 <400> 648 tgtccactga aggacattca attcaaacca tccagcatcc accaagtaat cgtgcatcga 60 cagagacata cagcacccca gctctgttag ccccatctga gtctaatgct accagcactg 120 120 <210> 649 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 649_SMAD4 <400> 649 cagagacata cagcacccca gctctgttag ccccatctga gtctaatgct accagcactg 60 ccaactttcc caacattcct gtggcttcca caagtgagtt ctagaatcag atgtagtcag 120 120 <210> 650 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 650_SMAD4 <400> 650 ccaactttcc caacattcct gtggcttcca caagtgagtt ctagaatcag atgtagtcag 60 caagttgagt tttcctaatc attgcttatt tatgtgtagt cacttggggg gaaactccaa 120 120 <210> 651 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 651_SMAD4 <400> 651 tatgaaatca taagatgaca tctatgaatg taccatgtta atgtcttctt gttcctctag 60 gtcagcctgc cagtatactg gggggcagcc atagtgaagg actgttgcag atagcatcag 120 120 <210> 652 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 652_SMAD4 <400> 652 gtcagcctgc cagtatactg gggggcagcc atagtgaagg actgttgcag atagcatcag 60 ggcctcagcc aggacagcag cagaatggat ttactggtca gccagctact taccatcata 120 120 <210> 653 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 653_SMAD4 <400> 653 ggcctcagcc aggacagcag cagaatggat ttactggtca gccagctact taccatcata 60 gtatgtacat actttaaaaa atcttttaaa tagttgagaa aaaagtaggc agcctttata 120 120 <210> 654 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 654_SMAD4 <400> 654 tagacagcac taccacctgg actggaagta ggactgcacc atacacacct aatttgcctc 60 accaccaaaa cggccatctt cagcaccacc cgcctatgcc gccccatccc ggacattact 120 120 <210> 655 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 655_SMAD4 <400> 655 acagcactac cacctggact ggaagtagga ctgcaccata cacacctaat ttgcctcacc 60 accaaaacgg ccatcttcag caccacccgc ctatgccgcc ccatcccgga cattactgta 120 120 <210> 656 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 656_SMAD4 <400> 656 ttactgaaag ttttagcatt agacaacttt tagtaaataa aaatggaatt tttgttgtct 60 tttctttagg gcctgttcac aatgagcttg cattccagcc tcccatttcc aatcatcctg 120 120 <210> 657 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 657_SMAD4 <400> 657 ggcctgttca caatgagctt gcattccagc ctcccatttc caatcatcct ggtaagtgta 60 tttcaaaatt gatttcctgt atttagattg atttagtggt gattgaaacg cacaaacaca 120 120 <210> 658 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 658_SMAD4 <400> 658 caagtgaaag ccttatatct ttctcatggg aggatgttct ttcccattta tttcctatag 60 ctcctgagta ttggtgttcc attgcttact ttgaaatgga tgttcaggta ggagagacat 120 120 <210> 659 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 659_SMAD4 <400> 659 ctcctgagta ttggtgttcc attgcttact ttgaaatgga tgttcaggta ggagagacat 60 ttaaggttcc ttcaagctgc cctattgtta ctgttgatgg atacgtggac ccttctggag 120 120 <210> 660 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 660_SMAD4 <400> 660 ttaaggttcc ttcaagctgc cctattgtta ctgttgatgg atacgtggac ccttctggag 60 gagatcgctt ttgtttgggt caactctcca atgtccacag gacagaagcc attgagagag 120 120 <210> 661 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 661_SMAD4 <400> 661 gagatcgctt ttgtttgggt caactctcca atgtccacag gacagaagcc attgagagag 60 caaggtattg attgtatagt cagatagtta ctttaaaaaa ttgagcatag tacattgtct 120 120 <210> 662 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 662_SMAD4 <400> 662 caaggtattg attgtatagt cagatagtta ctttaaaaaa ttgagcatag tacattgtct 60 tttattcaag gttatgtttt cccatgtaca ttatatgtgt tcttaaatat aaataaagga 120 120 <210> 663 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 663_SMAD4 <400> 663 actaaaattt aatttaaaat acttatcaag ataaaatgta atttcttttt tcttcctaag 60 gttgcacata ggcaaaggtg tgcagttgga atgtaaaggt gaaggtgatg tttgggtcag 120 120 <210> 664 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 664_SMAD4 <400> 664 gttgcacata ggcaaaggtg tgcagttgga atgtaaaggt gaaggtgatg tttgggtcag 60 gtgccttagt gaccacgcgg tctttgtaca gagttactac ttagacagag aagctgggcg 120 120 <210> 665 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 665_SMAD4 <400> 665 gtgccttagt gaccacgcgg tctttgtaca gagttactac ttagacagag aagctgggcg 60 tgcacctgga gatgctgttc ataagatcta cccaagtgca tatataaagg ttagttacaa 120 120 <210> 666 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 666_SMAD4 <400> 666 tgcacctgga gatgctgttc ataagatcta cccaagtgca tatataaagg ttagttacaa 60 ttttatttga atattttaga cttaaagctc tatttgttgt caaaagaatt gaaatctggg 120 120 <210> 667 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 667_SMAD4 <400> 667 tttttaatgt atggaatttt tctttatgaa ctcatagtat gaaatgtttt ttcttaaaag 60 gtctttgatt tgcgtcagtg tcatcgacag atgcagcagc aggcggctac tgcacaagct 120 120 <210> 668 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 668_SMAD4 <400> 668 gtctttgatt tgcgtcagtg tcatcgacag atgcagcagc aggcggctac tgcacaagct 60 gcagcagctg cccaggcagc agccgtggca ggaaacatcc ctggcccagg atcagtaggt 120 120 <210> 669 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 669_SMAD4 <400> 669 gcagcagctg cccaggcagc agccgtggca ggaaacatcc ctggcccagg atcagtaggt 60 ggaatagctc cagctatcag taagtatgct tttcattctt ttttaaaggt ataatagttg 120 120 <210> 670 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 670_SMAD4 <400> 670 ggaatagctc cagctatcag taagtatgct tttcattctt ttttaaaggt ataatagttg 60 atatttttat cttgatttac tcagttgatt agtttctttg agcagtaata gaaattaaag 120 120 <210> 671 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 671_SMAD4 <400> 671 tagggaggat gggaagagat caccctgtcc ctctgatgtc ttccaaatct tttctgttag 60 gtctgtcagc tgctgctgga attggtgttg atgaccttcg tcgcttatgc atactcagga 120 120 <210> 672 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 672_SMAD4 <400> 672 gtctgtcagc tgctgctgga attggtgttg atgaccttcg tcgcttatgc atactcagga 60 tgagttttgt gaaaggctgg ggaccggatt acccaagaca gagcatcaaa gaaacacctt 120 120 <210> 673 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 673_SMAD4 <400> 673 tgagttttgt gaaaggctgg ggaccggatt acccaagaca gagcatcaaa gaaacacctt 60 gctggattga aattcactta caccgggccc tccagctcct agacgaagta cttcatacca 120 120 <210> 674 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 674_SMAD4 <400> 674 gctggattga aattcactta caccgggccc tccagctcct agacgaagta cttcatacca 60 tgccgattgc agacccacaa cctttagact gaggtctttt accgttgggg cccttaacct 120 120 <210> 675 <211> 120 <212> DNA <213> Artificial Sequence <220> <223> Probe 675_SMAD4 <400> 675 tgccgattgc agacccacaa cctttagact gaggtctttt accgttgggg cccttaacct 60 tatcaggatg gtggactaca aaatacaatc ctgtttataa tctgaagata tatttcactt 120 120

Claims (6)

  1. 대장암 환자로부터 분리된 혈액의 cfDNA 및 대장암 환자로부터 분리된 대장암 조직의 유전체 DNA 중 어느 하나 이상으로부터 하기 각 유전자 캡처를 위한 서열번호 1 내지 서열번호 675의 핵산 서열로 표시되는 프로브를 포함하는, 대장암 다빈도 변이 유전자 캡처용 프로브 세트:
    Figure 112022136593218-pat00017

  2. 제 1 항에 있어서,
    상기 cfDNA는 ctDNA를 포함하는 것인, 대장암 다빈도 변이 유전자 캡처용 프로브 세트.
  3. 제 1 항 또는 제 2 항에 따른 프로브 세트를 포함하는 NGS 분석을 위한 대장암 다빈도 변이 유전자 캡처용 조성물.
  4. 제 1 항 또는 제 2 항에 따른 프로브 세트를 포함하는 NGS (Next Generation Sequencing) 분석을 위한 대장암 다빈도 변이 유전자 캡처용 키트.
  5. 제 1 항 또는 제 2 항에 따른 프로브 세트를 대장암의 진단, 대장암 재발여부 또는 대장암에 대한 항암제 내성 획득 여부의 판단이 필요한 환자의 혈액 또는 대장암 환자로부터 분리된 대장암 조직의 유전체 DNA로부터 추출된 cfDNA와 혼합하여, 상기 각 프로브가 상응하는 서열의 해당 유전자에 혼성화하는 단계를 포함하는, 제 1 항 또는 제 2 항에 따른 프로브 세트를 이용한 상기 각 유전자 캡처 방법.
  6. 제 1 항 또는 제 2 항에 따른 프로브 세트를 대장암의 진단, 대장암 재발여부 또는 대장암에 대한 항암제 내성 획득 여부의 판단이 필요한 환자의 혈액 또는 대장암 환자로부터 분리된 대장암 조직의 유전체 DNA로부터 추출된 cfDNA와 혼합하여, 상기 각 프로브가 상응하는 cfDNA 서열에 혼성화하도록 하여, 상기 각 유전자를 캡처하는 단계; 및
    상기 캡처된 유전자에 대한 NGS 분석을 수행하여, 상기 각 유전자에 대한 핵산서열을 결정하는 단계를 포함하는, 대장암 재발여부 또는 대장암에 대한 항암제 내성 획득 여부의 판단에 필요한 정보를 제공하기 위한, 대장암 환자의 상기 각 유전자 핵산 서열 결정 방법.
KR1020200152781A 2019-11-14 2020-11-16 차세대 염기서열 분석을 이용한 대장암 관련 다빈도 유전자 변이 검출을 위한 프로브 세트 KR102529550B1 (ko)

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