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Analysis for microsatellite instability and mutations of the DNA mismatch repair gene hMLH1 in familial gastric cancer
Author(s) -
Keller Gisela,
Grimm Volker,
Vogelsang Holger,
Bischoff Petra,
Mueller James,
Siewert Jörg Rüdiger,
Höfler Heinz
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19961127)68:5<571::aid-ijc3>3.0.co;2-w
Subject(s) - microsatellite instability , cancer , dna mismatch repair , genetics , microsatellite , dna repair , genome instability , mutation , medicine , biology , dna , dna damage , gene , allele
We examined 30 gastric‐cancer patients with a varying degree of family history of stomach cancer and/or synchronous gastric tumors for microsatellite instability. We observed microsatellite instability at at least 1 of 8 loci tested in tumors of 14/30 patients; of these 14, 8 had single locus alterations and 6 had alterations at at least half of the 8 loci. Among the patients with microsatellite instability at >=4 loci, 3 patients showed a strong familial clustering of gastric cancer. Mutation analysis of the DNA mismatch repair gene hMLH1 on paired non‐tumorous and tumor DNA from 10 patients 6 with microsatellite instability at 24 loci and 4 with an alteration at one locus, revealed a novel missense mutation, present in the normal and tumor DNA of one patient with microsatellite instability at multiple loci in his tumor. His family history of cancer included one second‐degree relative affected with gastric cancer. These data suggest that germline mutations in the hMLH1 gene occur in some gastric‐cancer patients and that in the majority of cases microsatellite instability in gastric tumors may be due to defects in other genes responsible for DNA replication fidelity than the hMLH1 . © 1996 Wiley‐Liss, Inc.