Topic
Replication Error Phenotype
About: Replication Error Phenotype is a research topic. Over the lifetime, 61 publications have been published within this topic receiving 18581 citations.
Papers
TL;DR: Data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with H NPCC suggest that hMSH2 is the HNPCC gene.
2,986 citations
TL;DR: It is shown that 12 per cent of colorectal carcinomas carry somatic deletions in poly(dA . dT) sequences and other simple repeats, and it is concluded that these mutations reflect a previously undescribed form of carcinogenesis in the colon mediated by a mutation in a DNA replication factor resulting in reduced fidelity for replication or repair (a 'mutator mutation').
Abstract: Spontaneous errors in DNA replication have been suggested to play a significant role in neoplastic transformation and to explain the chromosomal alterations seen in cancer cells. A defective replication factor could increase the mutation rate in clonal variants arising during tumour progression, but despite intensive efforts, increases in tumour cell mutation rates have not been unambiguously shown. Here we use an unbiased genomic fingerprinting technique to show that 12 per cent of colorectal carcinomas carry somatic deletions in poly(dA.dT) sequences and other simple repeats. We estimate that cells from these tumours can carry more than 100,000 such mutations. Only tumours with affected poly(dA.dT) sequences carry mutations in the other simple repeats examined, and such mutations can be found in all neoplastic regions of multiple tumours from the same patient, including adenomas. Tumours with these mutations show distinctive genotypic and phenotypic features. We conclude that these mutations reflect a previously undescribed form of carcinogenesis in the colon (predisposition to which may be inherited) mediated by a mutation in a DNA replication factor resulting in reduced fidelity for replication or repair (a 'mutator mutation').
2,904 citations
Johns Hopkins University1, University of Helsinki2, National Institutes of Health3, University of Denver4, Los Alamos National Laboratory5, Fred Hutchinson Cancer Research Center6, University of Texas Health Science Center at San Antonio7, Centre national de la recherche scientifique8, Memorial University of Newfoundland9, University of Auckland10, Creighton University11
TL;DR: Somatic as well as germline mutations of the gene were identified in RER+ tumor cells, and this mutS homolog is likely to be responsible for HNPCC.
2,430 citations
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.
2,017 citations
TL;DR: A true mutator phenotype exists in a subset of tumor cells, the responsible defect is likely to cause transitions and transversions in addition to microsatellite alterations, and a biochemical basis for this phenotype has been identified.
1,116 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2017 | 1 |
| 2013 | 1 |
| 2009 | 1 |
| 2007 | 1 |
| 2004 | 1 |
| 2003 | 1 |