title: Mutation spectrum in HNPCC in the Israeli population.
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.
authors.affiliation: Sharret Institute of Oncology, Hadassah-Hebrew University Medical Center, POB 12000, Kyriat Hadassah, 91120, Jerusalem, Israel. yaelg@hadassah.org.il
authors.forename: Yael
authors.initials: Y
authors.lastname: Goldberg
authors.forename: Rinnat M
authors.initials: RM
authors.lastname: Porat
authors.forename: Inbal
authors.initials: I
authors.lastname: Kedar
authors.forename: Chen
authors.initials: C
authors.lastname: Shochat
authors.forename: Michal
authors.initials: M
authors.lastname: Sagi
authors.forename: Avital
authors.initials: A
authors.lastname: Eilat
authors.forename: Suzan
authors.initials: S
authors.lastname: Mendelson
authors.forename: Tamar
authors.initials: T
authors.lastname: Hamburger
authors.forename: Aviram
authors.initials: A
authors.lastname: Nissan
authors.forename: Ayala
authors.initials: A
authors.lastname: Hubert
authors.forename: Luna
authors.initials: L
authors.lastname: Kadouri
authors.forename: Eli
authors.initials: E
authors.lastname: Pikarski
authors.forename: Israela
authors.initials: I
authors.lastname: Lerer
authors.forename: Dvorah
authors.initials: D
authors.lastname: Abeliovich
authors.forename: Dani
authors.initials: D
authors.lastname: Bercovich
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
mesh_terms: D000328:Adult; D000465:Algorithms; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D044382:Population Groups; D012189:Retrospective Studies