WO2013002490A1 - Biomarqueur pour le diagnostic du cancer du sein - Google Patents
Biomarqueur pour le diagnostic du cancer du sein Download PDFInfo
- Publication number
- WO2013002490A1 WO2013002490A1 PCT/KR2012/003882 KR2012003882W WO2013002490A1 WO 2013002490 A1 WO2013002490 A1 WO 2013002490A1 KR 2012003882 W KR2012003882 W KR 2012003882W WO 2013002490 A1 WO2013002490 A1 WO 2013002490A1
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- WO
- WIPO (PCT)
- Prior art keywords
- breast cancer
- biomarker
- mamdc2
- gene
- present
- Prior art date
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57415—Specifically defined cancers of breast
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Definitions
- the present invention relates to a biomarker for diagnosing breast cancer, and in particular, provides a biomarker for diagnosing breast cancer comprising a specific DNA fragment or full-length DNA of MAMDC2.
- Breast cancer is the second most common cancer in the world, after lung cancer, and mortality is the fifth most dangerous cancer.
- early detection is more important than other cancers because cancer is difficult to cure once cancer cells invade surrounding tissues or begin to metastasize to lymph nodes.
- breast X-ray angiography and ultrasonography are used as preventive screening methods, and this method is most widely used to diagnose early breast cancer.
- breast x-ray angiography is a dense breast that is commonly found in Korean women because of the high fiber, the diagnosis rate is low, especially the younger women, even if a lot of mammary gland development rate is low.
- the use of X-rays does not rule out the possibility of developing breast cancer in the course of diagnosis.
- ultrasonography is used, but it is also difficult to distinguish between malignant and non-cancer tumors.
- diagnosis rate is increased by additionally using fine needle aspiration cytology and magnetic resonance imaging.
- fine needle aspiration cytology and magnetic resonance imaging Even if these methods are used to distinguish between normal and abnormal tissues in a morphological form, it is not easy to distinguish between cancerous and non-cancer tumors.
- breast cancer has been developed to diagnose breast cancer in a relatively molecular genetic way compared to other cancers. The biopsy will reveal the lesion by cutting the tissue and then undergo a primary surgery for removal.
- HER2 / neu also known as Human Epidermal Growth Factor Receptor 2, ErbB-2 or ERBB2
- ERBB2 Human Epidermal Growth Factor Receptor 2
- HER2 / neu also known as Human Epidermal Growth Factor Receptor 2, ErbB-2 or ERBB2
- In situ hybridization is used. If the cancer tissue found has an estrogen receptor, it is treated with an estrogen analogue such as Tamoxifen, and if the HER2 / neu gene is overexpressed, Herceptin commercialized with the HER2 / neu monoclonal antibody trastuzumab. Herceptin will be used to treat breast cancer.
- HER2 / neu gene the breast cancer specific diagnostic marker most useful for the diagnosis and treatment of breast cancer, is found in 20-35% of invasive breast cancers. therefore.
- Oncotype DX is a method for screening 16 breast cancer genes and 5 control genes by real-time quantitative PCR
- MammaPrint is a method for microarraying 70 genes.
- the present inventors found that the expression level of the MAMDC2 gene included in tissues, in particular the expression level of a specific region of the gene transcript, was significantly associated with breast cancer using NanoString's nCounter Analysis System using clinical tissues.
- a DNA fragment or full length DNA of the breast cancer gene is used as a biomarker for diagnosing breast cancer.
- breast cancer When the expression level of the DNA fragment of MAMDC2 or the full-length DNA, which is a gene constituting the biomarker for diagnosing breast cancer of the present invention, from the tissue of the sample is measured and compared with the expression level in normal tissues, breast cancer can be effectively diagnosed. Breast cancer can be treated early.
- 1 is a view showing the results of confirming the breast cancer diagnostic performance for MAMDC2.
- the present invention relates to a biomarker for diagnosing breast cancer using a specific DNA fragment or full-length DNA of a gene that is expressed more specifically than normal tissue in breast cancer tissues, the DNA fragment or full-length DNA of the MAMDC2 gene comprising the polynucleotide of SEQ ID NO: 1 I use it. Since the MAMDC2 gene is characterized in that it is expressed more specifically in breast cancer tissue than normal tissue, the full-length DNA of the gene may be used as a biomarker for diagnosing breast cancer, and in particular, the MAMDC2 gene including the polynucleotide of SEQ ID NO: 1 in the sample tissue. DNA fragments can also be used as biomarkers for breast cancer diagnosis because the amount of DNA fragments can indirectly measure the quantitative expression level of the MAMDC2 gene.
- the method for diagnosing breast cancer using the biomarker for diagnosing breast cancer of the present invention is not particularly limited as long as it is a method used in the art.
- NanoString's nCounter Analysis system is an analytical device capable of digital mRNA profiling. It has the advantage of not needing cDNA synthesis process or amplification process of target to be measured. Therefore, total RNA, cell lysates, blood The advantage is that it can be analyzed if only a simpler sample such as lysates or FFPE sample is prepared.
- a) total RNA from a sample's breast tissue is directly directed to an nCounter probe comprising a reporter probe and a capture probe.
- information on the MAMDC2 gene and the probe used as a biomarker for diagnosing breast cancer is shown in Table 1.
- the clinical tissue of breast cancer is Chungnam National University Hospital Korea National Resource Bank (IRB) through IRB approval of matched normal and cancer tissues in the vicinity of cancer tissues of the same patient as cancer tissues of breast cancer patients. of Korea), the tissues of 100 patients were used, and the breast cancer clinical tissues were kept frozen at -70 ° C. Extraction of total RNA from breast cancer clinical tissues was recommended using TRI REAGENT (MRC). Total RNA was extracted and dissolved in DEPC (RNase inhibitor) -treated water.
- DEPC RNase inhibitor
- MAMDC2 showed a decrease in expression in breast cancer tissues, and thus, MAMDC2 could be verified as a biomarker for diagnosing breast cancer.
- the breast cancer diagnostic biomarker (MAMDC2) of the present invention has a high specificity (95.7) and sensitivity ( 93.4).
- the present invention can effectively diagnose breast cancer, through which it is possible to treat breast cancer early.
- SEQ. ID. NO. 1 polynucleotide fragment of MAMDC2 gene: AGGGAGGTTATGTTGCCCTGGATGATATTTCATTCTCTCCTGTTCACTGCCAGAATCAGACAGAACTTCTGTTCAGTGCCGTGGAAGCCAGCTGCAATTT
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
La présente invention concerne un biomarqueur pour le diagnostic du cancer du sein, et plus particulièrement concerne un biomarqueur pour le diagnostic du cancer du sein, comprenant un fragment d'ADN spécifique ou un ADN de longueur totale de MAMDC2. Il est possible de diagnostiquer efficacement le cancer du sein par la mesure du niveau d'expression d'un fragment d'ADN ou d'un ADN de longueur totale de MAMDC2 qui est le gène constituant le biomarqueur de diagnostic pour le cancer du sein de la présente invention, à partir du tissu d'un échantillon, et la comparaison du résultat mesuré avec le niveau d'expression d'un tissu normal, et il est possible de traiter le cancer du sein à un stade précoce par ce procédé.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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KR10-2011-0065194 | 2011-06-30 | ||
KR1020110065194A KR101441013B1 (ko) | 2011-06-30 | 2011-06-30 | 유방암 진단용 바이오마커 |
Publications (1)
Publication Number | Publication Date |
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WO2013002490A1 true WO2013002490A1 (fr) | 2013-01-03 |
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PCT/KR2012/003882 WO2013002490A1 (fr) | 2011-06-30 | 2012-05-17 | Biomarqueur pour le diagnostic du cancer du sein |
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KR (1) | KR101441013B1 (fr) |
WO (1) | WO2013002490A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105624279A (zh) * | 2015-01-22 | 2016-06-01 | 香港中文大学深圳研究院 | 胃癌标记物、其表达和甲基化检测方法、试剂盒及应用 |
Families Citing this family (1)
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KR102424255B1 (ko) * | 2020-10-30 | 2022-07-22 | 경북대학교 산학협력단 | 인간 유방암 및 동물 유선암의 진단 및 악성도 평가를 위한 바이오마커로서 smp30의 용도 |
Citations (2)
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US20060194229A1 (en) * | 2005-01-25 | 2006-08-31 | Sky Genetics, Inc. | Cancer markers and detection methods |
WO2010127399A1 (fr) * | 2009-05-06 | 2010-11-11 | Walter And Eliza Hall Institute Of Medical Research | Profils d'expression génétique et leurs utilisations |
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US20120053080A1 (en) * | 2009-03-09 | 2012-03-01 | Juan Cui | Protein markers identification for gastric cancer diagnosis |
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- 2011-06-30 KR KR1020110065194A patent/KR101441013B1/ko active IP Right Grant
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2012
- 2012-05-17 WO PCT/KR2012/003882 patent/WO2013002490A1/fr active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060194229A1 (en) * | 2005-01-25 | 2006-08-31 | Sky Genetics, Inc. | Cancer markers and detection methods |
WO2010127399A1 (fr) * | 2009-05-06 | 2010-11-11 | Walter And Eliza Hall Institute Of Medical Research | Profils d'expression génétique et leurs utilisations |
Non-Patent Citations (2)
Title |
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DATABASE GENBANK 30 December 2010 (2010-12-30), accession no. M_153267.4 * |
MARELLA ET AL.: "Cytogenetic and cDNA microarray expression analysis of MCF 1 human breast cancer progression cell line", CANCER RESEARCH, vol. 69, 7 July 2009 (2009-07-07), pages 5946 - 5953 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105624279A (zh) * | 2015-01-22 | 2016-06-01 | 香港中文大学深圳研究院 | 胃癌标记物、其表达和甲基化检测方法、试剂盒及应用 |
Also Published As
Publication number | Publication date |
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KR101441013B1 (ko) | 2014-09-18 |
KR20130003708A (ko) | 2013-01-09 |
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