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CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer
DC Field | Value | Language |
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dc.contributor.author | Weisenberger, D J | - |
dc.contributor.author | Siegmund, K D | - |
dc.contributor.author | Campan, M | - |
dc.contributor.author | Young, J | - |
dc.contributor.author | Long, T I | - |
dc.contributor.author | Faasse, M A | - |
dc.contributor.author | Kang, G H | - |
dc.contributor.author | Widschwendter, M | - |
dc.contributor.author | Weener, D | - |
dc.contributor.author | Buchanan, D | - |
dc.contributor.author | Koh, H | - |
dc.contributor.author | Simms, S | - |
dc.contributor.author | Barker, M | - |
dc.contributor.author | Leggett, B | - |
dc.contributor.author | Levine, J | - |
dc.contributor.author | Kim, M J | - |
dc.contributor.author | French, A J | - |
dc.contributor.author | Thibodeau, S N | - |
dc.contributor.author | Jass, F | - |
dc.contributor.author | Haile, R | - |
dc.contributor.author | Laird, P W | - |
dc.date.accessioned | 2009-10-05 | - |
dc.date.available | 2009-10-05 | - |
dc.date.issued | 2006-06-25 | - |
dc.identifier.citation | Nat. Genet. 38(7), 787-793 (2006). | en |
dc.identifier.issn | 1061-4036 | - |
dc.identifier.uri | https://hdl.handle.net/10371/10052 | - |
dc.description.abstract | Aberrant DNA methylation of CpG islands has been widely observed in human colorectal tumors and is associated with gene silencing when it occurs in promoter areas. A subset of colorectal tumors has an exceptionally high frequency of methylation of some CpG islands, leading to the suggestion of a distinct trait referred to as 'CpG island methylator phenotype', or 'CIMP'. However, the existence of CIMP has been challenged. To resolve this continuing controversy, we conducted a systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology, involving 295 primary human colorectal tumors and 16,785 separate quantitative analyses. We found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAF mutation (odds ratio = 203). Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors. | en |
dc.language.iso | en | en |
dc.publisher | Nature Publishing Group | en |
dc.subject | Colorectal Neoplasms/*genetics | en |
dc.subject | DNA Repair/genetics | en |
dc.subject | DNA, Neoplasm/chemistry/genetics | en |
dc.subject | Epigenesis, Genetic | en |
dc.subject | Gene Silencing | en |
dc.subject | Genomic Instability | en |
dc.subject | Humans | en |
dc.subject | Microsatellite Repeats | en |
dc.subject | Models, Genetic | en |
dc.subject | Phenotype | en |
dc.subject | Promoter Regions, Genetic | en |
dc.subject | Proto-Oncogene Proteins B-raf/*genetics | en |
dc.subject | CpG Islands | - |
dc.subject | DNA Methylation | - |
dc.subject | Mutation | - |
dc.title | CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | Weisenberger, Daniel J | - |
dc.contributor.AlternativeAuthor | Siegmund, Kimberly D | - |
dc.contributor.AlternativeAuthor | Campan, Mihaela | - |
dc.contributor.AlternativeAuthor | Young, Joanne | - |
dc.contributor.AlternativeAuthor | Long, Tiffany I | - |
dc.contributor.AlternativeAuthor | Faasse, Mark A | - |
dc.contributor.AlternativeAuthor | Kang, Gyeong Hoon | - |
dc.contributor.AlternativeAuthor | Widschwendter, Martin | - |
dc.contributor.AlternativeAuthor | Weener, Deborah | - |
dc.contributor.AlternativeAuthor | Buchanan, Daniel | - |
dc.contributor.AlternativeAuthor | Koh, Hoey | - |
dc.contributor.AlternativeAuthor | Simms, Lisa | - |
dc.contributor.AlternativeAuthor | Barker, Melissa | - |
dc.contributor.AlternativeAuthor | Leggett, Barbara | - |
dc.contributor.AlternativeAuthor | Levine, Joan | - |
dc.contributor.AlternativeAuthor | Kim, Myungjin | - |
dc.contributor.AlternativeAuthor | Thibodeau, Stephen N | - |
dc.contributor.AlternativeAuthor | French, Amy J | - |
dc.contributor.AlternativeAuthor | Jass, Jeremy | - |
dc.contributor.AlternativeAuthor | Laird, Peter W | - |
dc.contributor.AlternativeAuthor | Haile, Robert | - |
dc.identifier.doi | 10.1038/ng1834 | - |
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