Mutation of a <i>mutL</i> Homolog in Hereditary Colon Cancer

Nickolas Papadopoulos, Nicholas C. Nicolaides, Ying-Fei Wei(Human Genome Sciences (United States)), Steven M. Ruben(Human Genome Sciences (United States)), Kenneth C. Carter(Human Genome Sciences (United States)), C A Rosen(Human Genome Sciences (United States)), William A. Haseltine(Human Genome Sciences (United States)), Robert Fleischmann(Center for Genomic Science), Claire M. Fraser(Center for Genomic Science), Mark D. Adams(Center for Genomic Science), J. Craig Venter(Center for Genomic Science), Stanley R. Hamilton(Johns Hopkins University), Gloria M. Petersen(Johns Hopkins University), Patrice Watson(Creighton University), Henry T. Lynch(Creighton University), Païvi Peltomäki(University of Helsinki), Jukka‐Pekka Mecklin(University of Helsinki), Albert de la Chapelle(University of Helsinki), Kenneth W. Kinzler, Bert Vogelstein
Science
March 18, 1994
10.1126/science.8128251
Cited by 1,839

Abstract

Some cases of hereditary nonpolyposis colorectal cancer (HNPCC) are due to alterations in a mutS-related mismatch repair gene. A search of a large database of expressed sequence tags derived from random complementary DNA clones revealed three additional human mismatch repair genes, all related to the bacterial mutL gene. One of these genes (hMLH1) resides on chromosome 3p21, within 1 centimorgan of markers previously linked to cancer susceptibility in HNPCC kindreds. Mutations of hMLH1 that would disrupt the gene product were identified in such kindreds, demonstrating that this gene is responsible for the disease. These results suggest that defects in any of several mismatch repair genes can cause HNPCC.

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