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Familial Cancer
Published in: Familial Cancer 4/2008

01-12-2008

Mutation spectrum in HNPCC in the Israeli population

Authors: 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

Published in: Familial Cancer | Issue 4/2008

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Abstract

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.
Footnotes
1
http://​genome.​ucsc.​edu: (GenBank Accession nos. NM000249, NM000251, and NM000179 for MLH1, MSH2, and MSH6, respectively).
 
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Metadata
Title
Mutation spectrum in HNPCC in the Israeli population
Authors
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
Publication date
01-12-2008
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 4/2008
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-008-9191-y

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