Mutation spectrum in HNPCC in the Israeli population

Yael Goldberg, Rinnat M. Porat, Inbal Kedar, Chen Shochat, Michal Sagi, Avital Eilat, Suzan Mendelson, Tamar Hamburger, Aviram Nissan, Ayala Hubert, Luna Kadouri, Eli Pikarski, Israela Lerer, Dvorah Abeliovich, Dani Bercovich, Tamar Peretz

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish
Pages (from-to)309-317
Number of pages9
JournalFamilial Cancer
Issue number4
StatePublished - Dec 2008
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements This work was supported, in part, by the Israeli Cancer Association. We Thank Dr. Propping from the Institute of Human Genetics, University of Bonn, for detecting the mutation in one of the patients described in the present study.


  • Ashkenazi
  • Colorectal cancer
  • Israeli
  • Lynch
  • MMR
  • MSI
  • Oncogenetic


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