DNA methylation predicts recurrence from resected stage III proximal colon cancer.
DNA methylation predicts recurrence from resected stage III proximal colon cancer.
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DNA甲基化可预测切除的III期近端结肠癌的复发。
DOI：
10.1002/cncr.25737
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发表时间：
2011-05-01
期刊：
影响因子：
6.2
通讯作者：
Issa, Jean-Pierre J.
中科院分区：
文献类型：
--
作者：
Ahn, Joong Bae;Chung, Woon Bok;Maeda, Osamu;Shin, Sang Joon;Kim, Hyun Soo;Chung, Hyun Chul;Kim, Nam Kyu;Issa, Jean-Pierre J.
在结直肠癌(CRC)中，DNA甲基化异常定义了不同的亚型，称为CpG岛甲基化表型1(CIMP1)、CIMP2和CIMP阴性。我们评估了这一分类在预测切除的3期结直肠癌复发和无病生存(DFS)中的作用。我们分析了161名患者的散发性癌症。我们使用亚硫酸盐焦磷酸测序法检测了2个全局DNA甲基化标记(LINE-1，Alu)和9个基因座(MINT1，MINT2，MINT31，P16，hMLH1，P14，SFRP1，SFRP2和Wnt5A)的甲基化情况。我们检测了BRAF和KRAS的突变。基因高甲基化聚集在离散的患者组中，表明CIMP的存在。K-Means聚类分析发现3个离散亚组：CIMP1(N=22，13.7%)与近端部位和BRAF突变相关，CIMP2(N=40，24.8%)与KRAS突变相关，CIMP阴性(N=99，61.5%)与远端部位相关。在近端结直肠癌中，CIMP1与较高的复发率(53%、18%和26%)和较差的无病生存率(DFS)相关(P=0.015)。同样在近端结直肠癌中，复发患者的LINE-1甲基化水平低于未复发患者(P=.049)。在多因素分析中，CIMP1和LINE1低甲基化是影响近端结直肠癌患者DFS的独立预后因素(K均值聚类分析P=0.008，1号线甲基化状态P=0.040)。DNA甲基化是复发的一个有用的生物标志物，在切除的3期结直肠癌近端但不是远端。然而，由于CIMP1病例在远端结直肠癌中的数量很少，需要进一步的研究来验证我们的发现。
In colorectal cancer (CRC), DNA methylation anomalies define distinct subgroups termed CpG Island Methylator Phenotype 1, (CIMP1), CIMP2 and CIMP-negative. We evaluated the role of this classification in predicting recurrences and disease-free survival (DFS) in resected stage 3 CRC. We analyzed sporadic cancers from 161 patients. We used bisulfite-pyrosequencing to examine methylation of 2 global DNA methylation markers (LINE-1, Alu) and 9 loci (MINT1, MINT2, MINT31, P16, hMLH1, P14, SFRP1, SFRP2, and WNT5A). We assayed for mutations in BRAF and KRAS. Gene hypermethylation clustered in discrete groups of patients indicating the presence of CIMP. K-means clustering analysis identified 3 discrete subgroups; CIMP1 (N=22, 13.7%) associated with proximal location and BRAF mutations, CIMP2 (N=40, 24.8%) associated with KRAS mutations and CIMP-negative (N=99, 61.5%) associated with distal location. In proximal CRC, CIMP1 was correlated with a higher recurrence rate (53% for CIMP1, 18% for CIMP2 and 26% for CIMP-negative) and a worse disease free survival (DFS) (P= .015). Also in proximal CRC, LINE-1 methylation was lower in patients who recurred compared to those who did not recur (P= .049). In multivariate analysis, CIMP1 and low LINE1 methylation were independent prognostic factors for DFS in proximal CRC (P= .008 for classification by K means clustering analysis, P= .040 for LINE-1 methylation status). DNA methylation is a useful biomarker of recurrence in resected stage 3 proximal but not distal CRC. However, as the number of CIMP1 cases was small in distal CRC, further study is required to validate our findings.
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DOI：
10.1073/pnas.0704652104
发表时间：
2007-11-20
影响因子：
11.1
作者：
Shen, Lanlan;Toyota, Minoru;Issa, Jean-Pierre J.
通讯作者：
Issa, Jean-Pierre J.
影响因子：
11.2
作者：
Samowitz, WS;Sweeney, C;Slattery, ML
通讯作者：
Slattery, ML
影响因子：
2.7
作者：
Colella, S;Shen, L;Krahe, R
通讯作者：
Krahe, R
影响因子：
2.8
作者：
Azzoni, Cinzia;Bottarelli, Lorena;Sarli, Leopoldo
通讯作者：
Sarli, Leopoldo
影响因子：
56.9
作者：
Gaudet, F;Hodgson, JG;Jaenisch, R
通讯作者：
Jaenisch, R