P53 MUTATIONS IN HUMAN CANCERS
P53 MUTATIONS IN HUMAN CANCERS
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DOI：
10.1126/science.1905840
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发表时间：
1991-07-05
期刊：
影响因子：
56.9
通讯作者：
HARRIS, CC
中科院分区：
文献类型：
--
作者：
HOLLSTEIN, M;SIDRANSKY, D;HARRIS, CC
p53肿瘤抑制基因的进化保守密码子中的突变在多种类型的人类癌症中是常见的。p53突变谱在结肠癌、肺癌、食道癌、乳腺癌、肝癌、脑癌、网状内皮组织癌和造血组织癌中不同。对这些突变的分析可以为这些不同肿瘤的病因学和p53特定区域的功能提供线索。在结肠、脑和淋巴恶性肿瘤中，转换占主导地位，而G：C至T：A颠换是在肺癌和肝癌中观察到的最常见的替换。A：T碱基对突变在食道癌中比在其他实体瘤中更常见。结肠直肠癌、脑肿瘤、白血病和淋巴瘤中的大多数转变位于CpG二核苷酸突变热点。肺癌、乳腺癌和食管癌中的G到T颠换分布在许多密码子中。在来自黄曲霉毒素B1和B型肝炎病毒都是癌症危险因素的地理区域的人的肝肿瘤中，大多数突变发生在密码子249的一个核苷酸对上。这些差异可能反映了外源性和内源性因素对人类致癌的病因学贡献。
Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis.