DNA mismatch repair genes and colorectal cancer.
Positional cloning and linkage analysis have shown that inactivation of one of the mismatch repair genes (hMLH1, hMSH2, hPMS1, hPMS2, GTBP/hMSH6) is responsible for the microsatellite instability or replication error (RER+) seen in more than 90% of hereditary nonpolyposis colorectal cancers (HNPCC)...
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| Format: | Journal article |
| Language: | English |
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2000
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| _version_ | 1797097383256915968 |
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| author | Wheeler, J Bodmer, W Mortensen, N |
| author_facet | Wheeler, J Bodmer, W Mortensen, N |
| author_sort | Wheeler, J |
| collection | OXFORD |
| description | Positional cloning and linkage analysis have shown that inactivation of one of the mismatch repair genes (hMLH1, hMSH2, hPMS1, hPMS2, GTBP/hMSH6) is responsible for the microsatellite instability or replication error (RER+) seen in more than 90% of hereditary nonpolyposis colorectal cancers (HNPCC) and 15% of sporadic RER+ colorectal cancers. In HNPCC, a germline mutation (usually in hMLH1 or hMSH2) is accompanied by one further event (usually allelic loss) to inactivate a mismatch repair gene. In contrast, somatic mutations in the mismatch repair genes are not frequently found in sporadic RER+ colorectal cancers. Hypermethylation of the hMLH1 promoter region has recently been described, and this epigenetic change is the predominant cause of inactivation of mismatch repair genes in sporadic RER+ colorectal and other cancers. Inactivation of a mismatch repair gene may occur early (before inactivation of the APC gene) and produce a raised mutation rate in a proportion of HNPCC patients, and these cancers will follow a different pathway to other RER+ cancers. However, it is likely that selection for escape from apoptosis is the most important feature in the evolution of an RER+ cancer. |
| first_indexed | 2024-03-07T04:54:42Z |
| format | Journal article |
| id | oxford-uuid:d63175f4-dafb-4435-8ad0-4444843755af |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:54:42Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:d63175f4-dafb-4435-8ad0-4444843755af2022-03-27T08:31:38ZDNA mismatch repair genes and colorectal cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d63175f4-dafb-4435-8ad0-4444843755afEnglishSymplectic Elements at Oxford2000Wheeler, JBodmer, WMortensen, NPositional cloning and linkage analysis have shown that inactivation of one of the mismatch repair genes (hMLH1, hMSH2, hPMS1, hPMS2, GTBP/hMSH6) is responsible for the microsatellite instability or replication error (RER+) seen in more than 90% of hereditary nonpolyposis colorectal cancers (HNPCC) and 15% of sporadic RER+ colorectal cancers. In HNPCC, a germline mutation (usually in hMLH1 or hMSH2) is accompanied by one further event (usually allelic loss) to inactivate a mismatch repair gene. In contrast, somatic mutations in the mismatch repair genes are not frequently found in sporadic RER+ colorectal cancers. Hypermethylation of the hMLH1 promoter region has recently been described, and this epigenetic change is the predominant cause of inactivation of mismatch repair genes in sporadic RER+ colorectal and other cancers. Inactivation of a mismatch repair gene may occur early (before inactivation of the APC gene) and produce a raised mutation rate in a proportion of HNPCC patients, and these cancers will follow a different pathway to other RER+ cancers. However, it is likely that selection for escape from apoptosis is the most important feature in the evolution of an RER+ cancer. |
| spellingShingle | Wheeler, J Bodmer, W Mortensen, N DNA mismatch repair genes and colorectal cancer. |
| title | DNA mismatch repair genes and colorectal cancer. |
| title_full | DNA mismatch repair genes and colorectal cancer. |
| title_fullStr | DNA mismatch repair genes and colorectal cancer. |
| title_full_unstemmed | DNA mismatch repair genes and colorectal cancer. |
| title_short | DNA mismatch repair genes and colorectal cancer. |
| title_sort | dna mismatch repair genes and colorectal cancer |
| work_keys_str_mv | AT wheelerj dnamismatchrepairgenesandcolorectalcancer AT bodmerw dnamismatchrepairgenesandcolorectalcancer AT mortensenn dnamismatchrepairgenesandcolorectalcancer |