KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer
KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer
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DOI：
10.1158/1078-0432.ccr-10-1720
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发表时间：
2011-03-01
影响因子：
11.5
通讯作者：
Sieber, Oliver M.
中科院分区：
文献类型：
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作者：
Tie, Jeanne;Lipton, Lara;Sieber, Oliver M.
目的：癌基因突变有助于结直肠癌的发展。我们寻找癌基因突变谱之间的差异，从不同的网站和评估这些作为标志物的大肠癌转移复发situofrelations.Experimental Design：100结直肠癌转移进行了筛选突变19个癌基因，并进一步61转移和87匹配的原发癌进行了分析，基因与确定的突变。比较了（a）肝（n = 65）、肺（n = 50）和脑（n = 46）转移瘤，（B）转移瘤和匹配的原发性癌症，以及（c）转移瘤和独立的原发性癌症队列（n = 604）之间的突变患病率。结果：在结直肠癌转移灶中，19个癌基因中有4个检测到突变：BRAF（3.1%）、KRAS（48.4%）、NRAS（6.2%）和PIK 3CA（16.1%）。肺转移瘤（62.0%）和脑转移瘤（56.5%）的KRAS突变率显著高于肝转移瘤（32.3%; P = 0.003）。同一个体原发癌和转移癌的突变状态高度一致。与独立原发癌相比，肺转移癌和脑转移癌中KRAS突变更常见（P < 0.005），而肝转移癌中KRAS突变相似。相应地，KRAS突变与肺复发（HR = 2.1; 95%CI，1.2至3.5，P = 0.007），但不是肝复发的患者从维克托trial.Conclusions：KRAS突变似乎与转移在特定的网站，肺和脑，结直肠癌患者。我们的数据强调了体细胞突变为监测策略提供信息的潜力。临床癌症研究; 17（5）; 1122-30。（C）2011年《非洲标准化评论》。
Purpose: Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse.Experimental Design: One hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial.Results: In colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P < 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial.Conclusions: KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies. Clin Cancer Res; 17(5); 1122-30. (C)2011 AACR.