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Showing papers by "Robert D. Fleischmann published in 1994"

Journal Article•DOI•
Mutation of a mutL homolog in hereditary colon cancer

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Nickolas Papadopoulos1, Nicholas C. Nicolaides1, Ying Fei Wei2, Steven M. Ruben2, Kenneth C. Carter2, Craig A. Rosen2, William A. Haseltine2, Robert D. Fleischmann3, Claire M. Fraser3, Mark Raymond Adams3, J. Craig Venter3, Stanley R. Hamilton1, Gloria M. Petersen1, Patrice Watson4, Henry T. Lynch4, Päivi Peltomäki5, Jukka-Pekka Mecklin5, Albert de la Chapelle5, Kenneth W. Kinzler1, Bert Vogelstein1 •
Johns Hopkins University1, GlaxoSmithKline2, J. Craig Venter Institute3, Creighton University4, University of Helsinki5
18 Mar 1994-Science
TL;DR: 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, demonstrating that this gene is responsible for HNPCC.
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.

1,903 citations

Journal Article•DOI•
Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.

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Nicholas C. Nicolaides1, Nickolas Papadopoulos1, Bo Liu1, Ying Fei Weit2, Kenneth C. Carter2, Steven M. Ruben2, Craig A. Rosen2, William A. Haseltine2, Robert D. Fleischmann3, Claire M. Fraser3, Mark Raymond Adams3, J. Craig Venter3, Malcolm G. Dunlop4, Stanley R. Hamilton1, Gloria M. Petersen1, Albert de la Chapelle5, Bert Vogelstein1, Kenneth W. Kinzler1 •
Johns Hopkins University1, GlaxoSmithKline2, J. Craig Venter Institute3, Western General Hospital4, University of Helsinki5
01 Sep 1994-Nature
TL;DR: Two additional homologues of the prokaryotic mutL gene were found to be mutated in the germline of HNPCC patients, which doubles the number of genes implicated in H NPCC and may help explain the relatively high incidence of this disease.
Abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is one of man's commonest hereditary diseases. Several studies have implicated a defect in DNA mismatch repair in the pathogenesis of this disease. In particular, hMSH2 and hMLH1 homologues of the bacterial DNA mismatch repair genes mutS and mutL, respectively, were shown to be mutated in a subset of HNPCC cases. Here we report the nucleotide sequence, chromosome localization and mutational analysis of hPMS1 and hPMS2, two additional homologues of the prokaryotic mutL gene. Both hPMS1 and hPMS2 were found to be mutated in the germline of HNPCC patients. This doubles the number of genes implicated in HNPCC and may help explain the relatively high incidence of this disease.

1,587 citations