Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands

被引:198
作者
van Rijnsoever, M [1 ]
Grieu, F [1 ]
Elsaleh, H [1 ]
Joseph, D [1 ]
Iacopetta, B [1 ]
机构
[1] Univ Western Australia, Dept Surg, Nedlands, WA 6907, Australia
关键词
D O I
10.1136/gut.51.6.797
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and aims: A subgroup of colorectal cancers (CRC) referred to as the CpG island methylator 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 MDR1 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.
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页码:797 / 802
页数:6
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