EP2630496A1 - Verfahren zum diagnostizieren aneuploider kolorektaler tumore - Google Patents
Verfahren zum diagnostizieren aneuploider kolorektaler tumoreInfo
- Publication number
- EP2630496A1 EP2630496A1 EP11776144.5A EP11776144A EP2630496A1 EP 2630496 A1 EP2630496 A1 EP 2630496A1 EP 11776144 A EP11776144 A EP 11776144A EP 2630496 A1 EP2630496 A1 EP 2630496A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- protein
- aneuploid
- colorectal
- hdac2
- txnl1
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- 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
- G01N33/57419—Specifically defined cancers of colon
-
- 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
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/978—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
- G01N2333/98—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
Definitions
- the invention relates to a method for diagnosing aneuploid colorectal tumors.
- Colorectal carcinomas are the third most common tumors in the Western world. At an early stage, this disease is curable. The risk of recurrence and metastasis is higher at advanced stage. The high death rate in colorectal cancer can be successfully reduced by detecting this disease at an earlier stage. However, despite various screening programs, 50% of all tumors are detected at an advanced stage. This demonstrates the clinical need for personalized monitoring and therapy to improve the patient's prognosis.
- CRC Colorectal carcinoma
- MSI Microsatellite Instability
- MSI is responsible for 15-20% of all sporadic colorectal cancers.
- MMR mismatch repair system
- TGFBR2 Transforming Growth Factor Beta Receptor 2
- MSI tumors have diploid cell populations with few if any karyotypic changes and show a favorable clinical prognosis.
- CIN are characterized by aneuploidy.
- these aneuploid carcinomas show various chromosomal aberrations.
- Aneuploid carcinomas are responsible for 80% of all tumors in sporadic colon carcinoma and have a much worse clinical prognosis.
- a high rate of recurrence and a low life expectancy are to be expected when diagnosing this disease at a late stage. Early diagnosis would significantly improve the prognosis of patients. To date, there are no reliable biomarkers that allow the individual prognosis of colorectal carcinomas.
- the present invention relates to a method of diagnosing aneuploid colorectal tumors, characterized by assaying a suitably processed tissue sample for a significantly increased presence of the protein HDAC2.
- the method of the invention is characterized by assaying the appropriately processed tissue sample for a significantly reduced presence of the protein CAPZA1 and / or TXNL1. In another embodiment, the method of the invention is characterized by examining the reclaimed tissue sample by creating a protein expression profile.
- the method of the present invention permits the identification of aneuploid colorectal carcinomas in which there is a significantly increased presence of the protein HDAC2 and, if applicable, significantly reduced presence of the protein CAPZA1 and / or TXNL1 in the tissue sample of an individual compared to a sample of a healthy intestinal mucosa Presence of an aneuploid colorectal carcinoma in an individual indicates.
- the present invention relates to the use of a kit in one of the above-mentioned methods according to the invention, wherein the kit comprises reagents which are specific for the detection of HDAC2, CAPZA1 and / or TXNL1 proteins.
- the reagents of the kit may be, for example, antibodies which specifically bind to the abovementioned HDAC2, CAPZA1 and / or TXNL1 proteins, or labeled nucleic acid probes which bind to the mRNA which encode the abovementioned proteins.
- an identification of aneuploid colorectal carcinomas of an individual is possible. Detection of the HDAC2, CAPZAl and / or TXNLl proteins in colorectal carcinoma compared to the healthy intestinal mucosa of patients has been identified as a reliable feature for the presence of aneuploid colorectal tumors.
- the invention will be described in more detail with reference to a preferred embodiment, but without limiting the scope of the present invention.
- CAPZA1 is a member of the F-actin capping protein alpha family and encodes the alpha subunit of the actin binding protein. This protein regulates and protects the growth of the actin filament by covering the ends of growing actin filaments. So far, no association between CAPZAl and genomic instability in cancer has been identified. It is conceivable that CAPZAl has an impact on the integrity of actin filaments and actin binding proteins necessary for safe chromosome separation. Therefore, decreased CAPZAI expression could be a cause of genomic instability and lead to tumor development.
- the TXNL1 gene encodes a protein belonging to the thioredoxin family of small redox-active proteins. It is involved in the cellular response to stress and regulates redox status in higher eukaryotes. It is known that overexpression of TXNL1 can increase repressor function by binding to transcription factor B-Myb. Significant underexpression of TXNL1 in aneuploid colorectal carcinoma was found in this study.
- HDAC2 in contrast to TXNL1 and CAPZA1, is more highly expressed in aneuploid colorectal cancer cell lines.
- HDAC2 belongs to the histone deacetylase family and plays an important role in transcriptional regulation and cell cycle development. Although overexpression in various tumor tissues, including colon carcinomas, has already been demonstrated, it has been shown for the first time that significant overexpression of HDAC2 is evidence of aneuploid colorectal cancer.
- colorectal carcinomas and adjacent healthy mucosal specimens were randomly taken from 97 patients (out of a total of 1840) who underwent surgery between 1994 and 2007. Patients who had undergone radiation were excluded. The material came from surgically removed material.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pathology (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Genetics & Genomics (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE201010048899 DE102010048899B8 (de) | 2010-10-19 | 2010-10-19 | Verfahren zum Diagnostizieren aneuploider kolorektaler Tumore |
PCT/EP2011/068244 WO2012052473A1 (de) | 2010-10-19 | 2011-10-19 | Verfahren zum diagnostizieren aneuploider kolorektaler tumore |
Publications (1)
Publication Number | Publication Date |
---|---|
EP2630496A1 true EP2630496A1 (de) | 2013-08-28 |
Family
ID=44883229
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP11776144.5A Ceased EP2630496A1 (de) | 2010-10-19 | 2011-10-19 | Verfahren zum diagnostizieren aneuploider kolorektaler tumore |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP2630496A1 (de) |
DE (1) | DE102010048899B8 (de) |
WO (1) | WO2012052473A1 (de) |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US5919657A (en) * | 1997-04-09 | 1999-07-06 | Incyte Pharmaceuticals, Inc. | Nucleic acids encoding human thioredoxin protein; related reagents |
EP1290446A2 (de) * | 2000-06-16 | 2003-03-12 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Verfahren zum identifizieren von bei der apoptose modifizierten proteinen |
WO2008099972A1 (ja) * | 2007-02-16 | 2008-08-21 | Shimadzu Corporation | 上皮性卵巣癌の組織型識別マーカー、及びそれを用いた組織型に基づく上皮性卵巣癌の罹患の識別法 |
-
2010
- 2010-10-19 DE DE201010048899 patent/DE102010048899B8/de not_active Expired - Fee Related
-
2011
- 2011-10-19 EP EP11776144.5A patent/EP2630496A1/de not_active Ceased
- 2011-10-19 WO PCT/EP2011/068244 patent/WO2012052473A1/de active Application Filing
Non-Patent Citations (2)
Title |
---|
ROPERO S ET AL: "A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition", NATURE GENETICS, NATURE PUBLISHING GROUP, NEW YORK, US, vol. 38, no. 5, 16 April 2006 (2006-04-16), pages 566 - 569, XP002401873, ISSN: 1061-4036, DOI: 10.1038/NG1773 * |
See also references of WO2012052473A1 * |
Also Published As
Publication number | Publication date |
---|---|
DE102010048899B8 (de) | 2012-06-14 |
WO2012052473A1 (de) | 2012-04-26 |
DE102010048899B3 (de) | 2012-03-01 |
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