Journal
JOURNAL OF PATHOLOGY
Volume 214, Issue 5, Pages 594-602Publisher
WILEY
DOI: 10.1002/path.2318
Keywords
colorectal cancer; methylator phenotype; CIMP; microsatellite instability; microarray
Funding
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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The CpG island methylator phenotype (CIMP) in colorectal tumours can be recognized by an increased frequency of aberrant methylation in a specific set of genomic loci. Because of the strong association of CIMP with high microsatellite instability (NISI-H), the identification of CIMP+ tumours within microsatellite stable (MSS) collorectal cancers may not be straightforward. To overcome this potential limitation, we have built an improved seven-locus set of methylation markers that includes CACNA1G, IGF2, RUNX3, HTR6, RIZ1, MINT31, and MAP1B. This new set of CIMP markers revealed a bimodal distribution of methylation frequencies in a group of 95 MSS colorectal cancers, which allowed a clearer separation between CIMP classes. Correlation of MSS CIMP+ tumours with bio-pathological traits revealed significant associations with location to the proximal colon, mucinous histology, BRAF mutation, and chromosomal stability. A potential trend towards an adverse prognosis of CIMP+ cases was associated with the high frequency of BRAF mutations present within this cohort of tumours. Microarray analysis revealed that CIMP+ tumours are characterized by a unique expression profile, a result that confirms that CIMP+ tumours represent a truly distinct molecular class within MSS colorectal cancers. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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