Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features.
Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features.
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DOI：
10.1186/1471-2407-10-227
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发表时间：
2010-05-21
期刊：
影响因子：
3.8
通讯作者：
Soong R
中科院分区：
文献类型：
--
作者：
Ang PW;Loh M;Liem N;Lim PL;Grieu F;Vaithilingam A;Platell C;Yong WP;Iacopetta B;Soong R
大多数对结直肠癌（CRC）CpG岛甲基表型（CIMP）（CRC）的研究是在相对较少的CPG部位进行的，我们在本研究中进行了CRC的全面DNA甲基化分析，目的是表征CIMP亚组。
在807个癌症相关基因中，使用28个正常结肠粘膜和91个连续CRC样品在807个癌症相关基因中的DNA甲基化。包括患者年龄，肿瘤部位，微卫星不稳定性（MSI），甲基化在内的特征BRAF和KRAS中的CPG岛和突变。
在肿瘤和正常组织之间，共有202个CpG位点的甲基化不同。与CIMP-L肿瘤相比，Mid（CIMP-M，14％）和CIMP-H（65％）。并显示出更频繁的KRAS和BRAF突变（p <0.001）。
全面的DNA甲基化分析确定了三个具有不同临床病理学和分子特征的CRC亚组。
Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
3.7
作者：
Nosho K;Irahara N;Shima K;Kure S;Kirkner GJ;Schernhammer ES;Hazra A;Hunter DJ;Quackenbush J;Spiegelman D;Giovannucci EL;Fuchs CS;Ogino S
通讯作者：
Ogino S
影响因子：
24.5
作者：
Ogino, S.;Cantor, M.;Fuchs, C. S.
通讯作者：
Fuchs, C. S.
影响因子：
7.5
作者：
Kawasaki, Takako;Ohnishi, Mutsuko;Ogino, Shuji
通讯作者：
Ogino, Shuji
影响因子：
22.4
作者：
HUBERT, LJ;LEVIN, JR
通讯作者：
LEVIN, JR