TITLE

Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands

AUTHOR(S)
van Rijnsoever, M.; Grieu, F.; Elsaleh, H.; Joseph, D.; Iacopetta, B.
PUB. DATE
December 2002
SOURCE
Gut;Dec2002, Vol. 51 Issue 6, p797
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: A subgroup of colorectal cancers (CRC) referred to as the CpG island methy- lator phenotype (CIMP+) shows simultaneous methylation of multiple CpG islands. The clinicopathological and molecular characteristics of this phenotype remain uncertain however. Methods: We analysed methylation of CpG islands in the p 16 and MDR 1 genes and MINT-2 clone in 275 stage II/III CRCs. Results: Concurrent methylation of two or more CpG islands was observed in 32% of cases and was considered to represent CIMP+. These were often poorly differentiated, had less TP53 mutations, and originated frequently in the proximal or higher stage CRC compared with CIMP- tumours (p<0.05 for each). CIMP+ had no prognostic significance in stage II or stage III CRC treated by surgery alone. hMLH1 methylated tumours comprised the majority (81%) of cases with microsatellite instability, were frequently observed in older female patients, were often poorly differentiated or CIMP+, and contained wild-type K-ras (p<0.05 for each). Females who were heterozygous or homozygous for the C677T MTHFR polymorphism were at increased risk of developing CIMP+ CRC (odds ratio 2.17, 95% confidence interval 1.03-4.57; p=0.037). Conclusions: These observations made in a relatively large unselected series of CRC support the notion that CIMP+ characterises a subgroup of tumours with distinctive phenotypic features.
ACCESSION #
9737549

 

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