Details

Autor(en) / Beteiligte

• Laird, Peter W
• Weisenberger, Daniel J
• Siegmund, Kimberly D
• Campan, Mihaela
• Young, Joanne
• Long, Tiffany I
• Faasse, Mark A
• Kang, Gyeong Hoon
• Widschwendter, Martin
• Weener, Deborah
• Buchanan, Daniel
• Koh, Hoey
• Simms, Lisa
• Barker, Melissa
• Leggett, Barbara
• Levine, Joan
• Kim, Myungjin
• French, Amy J
• Thibodeau, Stephen N
• Jass, Jeremy
• Haile, Robert

Titel

CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer

Ist Teil von

• Nature genetics, 2006-07, Vol.38 (7), p.787-793

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.