The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile
The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile
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DOI：
10.1002/path.2318
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发表时间：
2008-04-01
影响因子：
7.3
通讯作者：
Negrin, M.
中科院分区：
文献类型：
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作者：
Ferracin, M.;Gafa, R.;Negrin, M.
结直肠肿瘤中的 CpG 岛甲基化表型 (CIMP) 可以通过一组特定基因组位点中异常甲基化频率的增加来识别。由于 CIMP 与高微卫星不稳定性 (NISI-H) 密切相关，因此微卫星稳定 (MSS) 结直肠癌中 CIMP+ 肿瘤的识别可能并不简单。为了克服这一潜在限制，我们构建了一套改进的七位点甲基化标记物，其中包括 CACNA1G、IGF2、RUNX3、HTR6、RIZ1、MINT31 和 MAP1B。这组新的 CIMP 标记揭示了一组 95 个 MSS 结直肠癌中甲基化频率的双峰分布，这使得 CIMP 类别之间的区分更加清晰。 MSS CIMP+ 肿瘤与生物病理学特征的相关性揭示了与近端结肠位置、粘液组织学、BRAF 突变和染色体稳定性的显着相关性。 CIMP+病例不良预后的潜在趋势与该肿瘤队列中存在的高频率 BRAF 突变有关。微阵列分析显示 CIMP+ 肿瘤具有独特的表达谱，这一结果证实 CIMP+ 肿瘤代表了 MSS 结直肠癌中真正独特的分子类别。版权所有 (C) 2008 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
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.