A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers.
A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers.
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DOI：
10.1053/j.gastro.2009.08.002
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发表时间：
2009-11
期刊：
影响因子：
29.4
通讯作者：
Ogino S
中科院分区：
文献类型：
--
作者：
Nosho K;Kure S;Irahara N;Shima K;Baba Y;Spiegelman D;Meyerhardt JA;Giovannucci EL;Fuchs CS;Ogino S
同步性结直肠肿瘤（同一患者中发现2种或2种以上原发癌）是由常见的遗传和环境因素引起的，因此可用于研究场效应。在一项前瞻性研究中，同步性结肠癌与对照孤立性癌症没有进行比较。我们分析了2项前瞻性队列研究中47例同步性结直肠癌患者和2021例孤立性结直肠癌（对照）的数据。分析肿瘤样品中LINE-1和16个CpG岛的甲基化（CACNA 1G、CDKN 2A [p16]、CRABP 1、IGF 2、MLH 1、NEUROG 1、RUNX 3、SOCS 1、CHFR、MGMT 1、IGFBP 3、MGMT、MINT 1、MINT 31、p14 [ARF]和WRN）;微卫星不稳定性（MSI）; CpG岛甲基化表型（CIMP）; 18 q杂合性缺失; KRAS、BRAF和PIK 3CA突变;以及β-连环蛋白、p53、p21、p27、细胞周期蛋白D1、脂肪酸合成酶和环氧合酶-2的表达。与孤立性结直肠癌患者相比，同步性结直肠癌患者的总生存时间缩短（对数秩p=0.0048;风险比[HR]=1.71; 95%置信区间[CI]=1.17-2.50; p=0.0053;多变量HR=1.47; 95% CI=1.00-2.17; p=0.049）。与孤立性肿瘤相比，同步性肿瘤更常包含BRAF突变（p=0.0041）、CIMP高（≥6/8甲基化CIMP标记物; p=0.013）和MSI高（p=0.037）。LINE-1的甲基化水平（斯皮尔曼r=0.82; p=0.0072）和CpG岛甲基化水平（p<0.0001）在来自相同个体的同步癌症对之间相关。同步结直肠癌在BRAF中有更频繁的突变，更频繁地被归类为CIMP-和MSI-高，并且比孤立结直肠癌预后更差。在同步癌症对中经常观察到类似的表观基因组和表观遗传事件，表明存在场效应。
Synchronous colorectal neoplasias (2 or more primary carcinomas identified in the same patient) are caused by common genetic and environmental factors and can therefore be used to study the field effect. Synchronous colon cancers have not been compared with control solitary cancers in a prospective study. We analyzed data collected from 47 patients with synchronous colorectal cancers and 2021 solitary colorectal cancers (controls) in 2 prospective cohort studies. Tumors samples were analyzed for methylation in LINE-1 and 16 CpG islands (CACNA1G, CDKN2A [p16], CRABP1, IGF2, MLH1, NEUROG1, RUNX3, SOCS1, CHFR,HIC1, IGFBP3, MGMT, MINT1, MINT31, p14 [ARF], and WRN); microsatellite instability (MSI); the CpG island methylator phenotype (CIMP); 18q loss of heterozygosity; KRAS, BRAF and PIK3CA mutations; and expression of β-catenin, p53, p21, p27, cyclin D1, fatty acid synthase, and cyclooxygenase-2. Compared to patients with solitary colorectal cancer, synchronous colorectal cancer patients had reduced overall survival time (log-rank p=0.0048; hazard ratio [HR]=1.71; 95% confidence interval [CI]=1.17–2.50; p=0.0053; multivariate HR=1.47; 95% CI=1.00–2.17; p=0.049). Compared to solitary tumors, synchronous tumors more frequently contained BRAF mutations (p=0.0041), CIMP-high (≥6/8 methylated CIMP markers; p=0.013), and MSI-high (p=0.037). Methylation levels of LINE-1 (Spearman r=0.82; p=0.0072) and levels of CpG island methylation (p<0.0001) correlated between synchronous cancer pairs from the same individuals. Synchronous colorectal cancers had more frequent mutations in BRAF, were more frequently categorized as CIMP- and MSI-high, and a worse prognosis than solitary colorectal cancers. Similar epigenomic and epigenetic events were frequently observed within a synchronous cancer pair, suggesting the presence of a field effect.
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影响因子：
9
作者：
ENKER, WE;DRAGACEVIC, S
通讯作者：
DRAGACEVIC, S
MLH1，MSH2和MSH6在多种结直肠癌的发展中的作用。
影响因子：
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影响因子：
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作者：
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