FREQUENT MUTATION OF THE P53 GENE IN HUMAN ESOPHAGEAL CANCER
FREQUENT MUTATION OF THE P53 GENE IN HUMAN ESOPHAGEAL CANCER
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DOI：
10.1073/pnas.87.24.9958
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发表时间：
1990-12-01
影响因子：
11.1
通讯作者：
HARRIS, CC
中科院分区：
文献类型：
--
作者：
HOLLSTEIN, MC;METCALF, RA;HARRIS, CC
在人类的脑、乳房、肺和结肠肿瘤中已检测到p53基因的序列变化，并已提出跨越编码区主要部分的p53突变使该基因的肿瘤抑制功能失活。据我们所知，在人类食道肿瘤中，既没有癌基因的转化突变，也没有肿瘤抑制基因的突变。我们用聚合酶链式反应扩增和直接测序的方法检测了4个人食管鳞癌细胞系和14个人食管鳞癌组织中p53基因外显子5、6、7、8和9的突变。2个细胞系和5个肿瘤标本中有1个突变等位基因(1个移码突变，6个错义突变)。所有检测到的错义突变都发生在以前在其他癌症中报道的突变的密码子或邻近密码子的G.cntdot.C碱基对上。在我们测试的三分之一的肿瘤中发现了异常的P53基因等位基因，这表明该基因的突变是食道鳞状细胞癌发病机制中常见的遗传事件。
Sequence alterations in the p53 gene have been detected in human tumors of the brain, breasts, lung, and colon, and it has been proposed that p53 mutations spanning a major portion of the coding region inactivate the tumor suppressor function of this gene. To our knowledge, neither transforming mutations in oncogenes nor mutations in tumor suppressor genes have been reported in human esophageal tumors. We examined four human esophageal carcinoma cell lines and 14 huamn esophageal squamous cell carcinomas by polymerase chain reaction amplification and direct sequencing for the presence of p53 mutations in exons 5, 6, 7, 8, and 9. Two cell lines and five of the tumor specimens contained a mutated allele (one frameshift and six missense mutations). All missense mutations detected occurred at G.cntdot.C base pairs in codons at or adjacent to mutations previously reported in other cancers. The identification of aberrant p53 gene alleles in one-third of the tumors we tested suggests that mutations at this locus are common genetic events in the pathogenesis of squamous cell carcinomas of the esophagus.