Home LiteratureArticle Details

PMID: 8261515 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer.

Cell ·Vol. 75 ·No. 6 ·1993-12-17 ·Pages 1215-25

Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomäki P, Sistonen P, Aaltonen LA, Nyström-Lahti M

Abstract

Recent studies have shown that a locus responsible for hereditary nonpolyposis colorectal cancer (HNPCC) is on chromosome 2p and that tumors developing in these patients contain alterations in microsatellite sequences (RER+ phenotype). We have used chromosome microdissection to obtain highly polymorphic markers from chromosome 2p16. These and other markers were ordered in a panel of somatic cell hybrids and used to define a 0.8 Mb interval containing the HNPCC locus. Candidate genes were then mapped, and one was found to lie within the 0.8 Mb interval. We identified this candidate by virtue of its homology to mutS mismatch repair genes. cDNA clones were obtained and the sequence used to detect germline mutations, including those producing termination codons, in HNPCC kindreds. Somatic as well as germline mutations of the gene were identified in RER+ tumor cells. This mutS homolog is therefore likely to be responsible for HNPCC.

MeSH Terms

Amino Acid Sequence Animals Base Sequence Brain/metabolism Cell Line Chromosome Banding Chromosome Mapping Chromosomes, Human, Pair 2 Colon/metabolism Colonic Neoplasms/genetics Colorectal Neoplasms, Hereditary Nonpolyposis/genetics Cricetinae DNA Primers DNA Repair/genetics DNA-Binding Proteins Fungal Proteins/genetics Gene Library Genetic Linkage Genetic Markers Humans Hybrid Cells In Situ Hybridization, Fluorescence Mice Molecular Sequence Data MutS Homolog 2 Protein Mutation Open Reading Frames Polymerase Chain Reaction Polymorphism, Genetic Proto-Oncogene Proteins/genetics Rats Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid

Chemicals

DNA Primers DNA-Binding Proteins Fungal Proteins Genetic Markers Proto-Oncogene Proteins Saccharomyces cerevisiae Proteins MSH2 protein, S cerevisiae MSH2 protein, human Msh2 protein, mouse Msh2 protein, rat MutS Homolog 2 Protein

Authors & Affiliations

10 authors, click to expand affiliations / ORCID

Leach F S

Johns Hopkins Oncology Center, Baltimore, Maryland 21231.

Nicolaides N C

Papadopoulos N

Liu B

Jen J

Parsons R

Peltomäki P

Sistonen P

Aaltonen L A

Nyström-Lahti M

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/0092-8674(93)90330-s

Published

1993-12-17

Pages

1215-25

Language

English

Region

United States

NLM ID

0413066

Subset

Grants

NCI NIH HHS · CA09320 · United States

NCI NIH HHS · CA35494 · United States

NCI NIH HHS · CA47527 · United States

Databases

GENBANK

L20821, L20822, L20823, L20888, L20889, L33709, S60904, S60905, S60924, U04045

External Links

PubMed source DOI: 10.1016/0092-8674(93)90330-s View journal details

Analysis Services

Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer.

Contact

WeChat Official Account