K-ras mutations and RASSF1A promoter methylation in colorectal cancer
K-ras mutations and RASSF1A promoter methylation in colorectal cancer
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DOI：
10.1038/sj.onc.1205466
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发表时间：
2002-05-23
期刊：
影响因子：
8
通讯作者：
Herman, JG
中科院分区：
文献类型：
--
作者：
van Engeland, M;Roemen, GMJM;Herman, JG
人类癌症的特征是遗传和表观遗传改变。在这项研究中，我们为散发性结直肠癌(CRC)中RAS信号的阻断提供了证据，要么是K-ras癌基因的遗传激活，要么是可能的肿瘤抑制基因RASSF1A的表观遗传沉默。对222例散发性结直肠癌石蜡包埋组织标本进行K-ras第12、13密码子激活突变和RASSF1A启动子甲基化分析。总体而言，222例癌组织中有87例(39%)发生K-ras基因突变，而222例癌组织中有45例(20%)发生RASSF1A甲基化。在222例大肠癌中，76例(34%)仅检测到K-ras基因突变。222例癌组织中有34例(15%)RASSF1A启动子甲基化。在222例大肠癌中，101例(46%)未发现K-ras突变，11例(5%)同时存在K-ras突变和RASSF1A甲基化。这些数据表明，大多数具有K-ras突变的癌组织缺乏RASSF1a启动子甲基化，该事件主要发生在K-ras野生型癌组织中(P=0.023，卡方检验)。
Human cancer is characterized by genetic and epigenetic alterations. In this study we provide evidence for the interruption of Ras signaling in sporadic colorectal cancer (CRC) by either genetic activation of the K-ras oncogene or epigenetic silencing of the putative tumor suppressor gene RASSF1A. Paraffin embedded tumor tissue samples from 222 sporadic CRC patients were analysed for K-ras codon 12 and codon 13 activating mutations and RASSF1A promoter hypermethylation. Overall, K-ras mutations were observed in 87 of 222 (39%) and RASSF1A methylation was observed in 45 of 222 (20%) of CRCs. Mutation of K-ras alone was detected in 76 of 222 (34%) CRCs. RASSF1A promoter methylation with wild-type K-ras was observed in 34 of 222 (15%) CRCs. In 101 of 222 (46%) CRCs neither K-ras mutations nor RASSF1A methylation was observed and 11 of 222 (5%) CRCs showed both K-ras mutations and RASSF1A methylation. These data show that the majority of the studied CRCs with K-ras mutations lack RASSF1A promoter methylation, an event which occurs predominantly in K-ras wild-type CRCs (P=0.023, Chi-square test).