Frequency and spectrum of mutations at codons 12 and 13 of the c-K-ras gene in human tumors.
Frequency and spectrum of mutations at codons 12 and 13 of the c-K-ras gene in human tumors.
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DOI：
10.1289/ehp.9193125
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发表时间：
1991-06
影响因子：
10.4
通讯作者：
Perucho M
中科院分区：
文献类型：
--
作者：
Capella G;Cronauer-Mitra S;Pienado MA;Perucho M
在400多个人类肿瘤中，已经确定了c-K-ras基因第12和13密码子的点突变频率。C-K-ras基因突变在约75%的胰腺癌(n=84)、40%的结肠癌(n=72)和244%的结肠癌(n=244)、30%的胆管癌(n=19)、25%的肺癌(n=92)中检测到c-K-ras基因突变，而在其他癌症，包括肝、胃和肾癌中检测到c-K-ras基因突变的频率较低。在乳腺癌、前列腺癌、食道癌和胆囊癌等肿瘤中没有发现突变。突变谱的比较分析表明，虽然G到A转换是胰腺和结直肠癌中最常见的突变，但G到T转换在肺癌中更常见。天冬氨酸第13位密码子突变(GGC-GAC)在结直肠癌中较常见，在胰腺癌和肺癌中较少见。胃肠道和呼吸道肿瘤中c-K-ras基因突变谱的差异提示不同的遗传毒物暴露。
The frequency of point mutations at codons 12 and 13 of the c-K-ras gene has been determined in a panel of more than 400 human tumors. Mutant c-K-ras genes were detected in about 75% of adenocarcinomas of the pancreas (n = 84); 40% of adenomas (n = 72) and carcinomas (n = 244) of the colon end rectum; 30% of carcinomas of the bile duct (n = 19); 25% of carcinomas of the lung (n = 92), and in lower frequency in other carcinomas, including liver, stomach, and kidney. No mutations were found in carcinomas of the breast, prostate, esophagus, and gall bladder, among others. Comparative analysis of the spectrum of mutations show that while G to A transitions were the most frequent mutations in pancreatic and colo-rectal tumors, G to T transversions were more prevalent in lung carcinomas. The aspartic acid mutation at codon 13 (GGC----GAC) was relatively frequent in colo-rectal tumors but rare in pancreatic and lung carcinomas. The differences in the mutation spectrum of the c-K-ras gene in cancers of the gastrointestinal and respiratory tracts are suggestive of differential exposure to genotoxic agents.