Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International society for gastrointestinal hereditary tumours collaborative study

Jae Gahb Park, Duck Woo Kim, Chang Won Hong, Byung Ho Nam, Young Kyoung Shin, Sung Hye Hong, Il Jin Kim, Seok Byung Lim, Melyssa Aronson, Marie Luise Bisgaard, Gregor J. Brown, John Burn, Elizabeth Chow, Peggy Conrad, Fiona Douglas, Malcolm Dunlop, James Ford, Marc S. Greenblatt, Jarvinen Heikki, Karl HeinimannElly L. Lynch, Finlay Macrae, Wendy C. McKinnon, Gabriela Möeslein, Benedito Mauro Rossi, Paul Rozen, Lyn Schofield, Carlos Vaccaro, Hans Vasen, Mary Velthuizen, Alessandra Viel, Juul Wijnen

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). Experimental Design: A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. Results: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared the distribution of the mismatch repair mutations in our study population with that in a control group, including all pathogenic mismatch repair mutations of the International Society for Gastrointestinal Hereditary Tumours database (excluding those in our study population). In patients with MSH2 mutations, patients with HNPCC-associated SBCs had fewer mutations in the MutL homologue interaction domain (2.9% versus 19.9%, P = 0.019) but an increased frequency of mutations in codons 626 to 733, a domain that has not previously been associated with a known function, versus the control group (26.5% versus 2.8%, P <0.001). Conclusions: In HNPCC patients, SBC can be the first and only cancer and may develop as soon as the early teens. The distribution of MSH2 mutations found in patients with HNPCC-associated SBCs significantly differed from that found in the control group (P <0.001).

Original languageEnglish
Pages (from-to)3389-3393
Number of pages5
JournalClinical Cancer Research
Volume12
Issue number11 I
DOIs
Publication statusPublished - Jun 1 2006

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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