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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Adenosine Triphosphatases*
-
Amino Acid Sequence
-
Bacterial Proteins / chemistry
-
Bacterial Proteins / genetics*
-
Base Sequence
-
Carrier Proteins
-
Chromosome Mapping
-
Chromosomes, Human, Pair 3*
-
Codon
-
Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
-
DNA Repair*
-
DNA-Binding Proteins*
-
Escherichia coli Proteins*
-
Female
-
Frameshift Mutation
-
Genes*
-
Genetic Markers
-
Humans
-
Male
-
Molecular Sequence Data
-
MutL Protein Homolog 1
-
MutL Proteins
-
MutS Homolog 2 Protein
-
Mutation
-
Neoplasm Proteins / chemistry
-
Neoplasm Proteins / genetics*
-
Nuclear Proteins
-
Open Reading Frames
-
Polymerase Chain Reaction
-
Proto-Oncogene Proteins / genetics
-
Sequence Deletion
-
Tumor Cells, Cultured
Substances
-
Adaptor Proteins, Signal Transducing
-
Bacterial Proteins
-
Carrier Proteins
-
Codon
-
DNA-Binding Proteins
-
Escherichia coli Proteins
-
Genetic Markers
-
MLH1 protein, human
-
MutL protein, E coli
-
Neoplasm Proteins
-
Nuclear Proteins
-
Proto-Oncogene Proteins
-
Adenosine Triphosphatases
-
MSH2 protein, human
-
MutL Protein Homolog 1
-
MutL Proteins
-
MutS Homolog 2 Protein