Mutation spectrum in HNPCC in the Israeli population
| Autor: | Israela Lerer, Rinnat M. Porat, Tamar Peretz, Suzan Mendelson, Dvorah Abeliovich, Aviram Nissan, Tamar Hamburger, Yael Goldberg, Ayala Hubert, Chen Shochat, Eli Pikarski, Inbal Kedar, Dani Bercovich, Avital Eilat, Michal Sagi, Luna Kadouri |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Cancer Research Sequence analysis Population Biology DNA Mismatch Repair Population Groups Genetics medicine Humans Israel education Gene Genetics (clinical) Retrospective Studies education.field_of_study Microsatellite instability medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis Ashkenazi jews Human genetics Pedigree Oncology Jews Mutation (genetic algorithm) Mutation DNA mismatch repair Female Algorithms |
| Zdroj: | Familial cancer. 7(4) |
| ISSN: | 1389-9600 |
| Popis: | Hereditary non-polyposis colon cancer is caused by mutations in DNA mismatch repair genes. The mutation spectrum in the Israeli population is poorly documented except for the c.1906G>C Ashkenazi founder mutation in the hMSH2 gene. To report our experience in HNPCC screening, the mutations detected and the clinical features among a cohort of Israeli patients. Diagnostic work-up was done in a multi-step process guided by clinical and ethnic information. Tumors of suspected patients were tested for microsatellite instability and immunohistochemistry. Based on tumor analyses, we proceeded to mutation screening by DHPLC followed by sequence analysis and multiplex ligase dependent probe amplification. Ashkenazi Jews were first tested for the c.1906G>C founder mutation. Of the 240 families, 24, including Arabs and Jews from different ethnic origins, were tested positive. All tumors that lost expression of mismatch repair proteins also showed microsatellite instability. There was evidence for involvement of hMSH2 (15) hMLH1 (6) and hMSH6 (3) genes. Mutations were identified in 17/24 (71%) patients: 6 Ashkenazi families harbored the c.1906G>C mutation. Eleven other mutations (2 nonsense, 3 splice site and 6 small deletions) were detected. Three of the mutations are novel. No gross deletions or insertions were detected. This is the first report that characterizes the profile of HNPCC in a cohort of patients in Israel. Tumor testing indicated that the 3 main MMR genes are involved, and that mutation spectrum is broad. |
| Databáze: | OpenAIRE |
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