Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations.
Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations.
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发表时间：
1991-08
期刊：
影响因子：
11.2
通讯作者：
M. Hollstein;L. Peri;A. Mandard;J. Welsh;R. Montesano;R. Metcalf;M. Bak;Curtis C. Harris
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文献类型：
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作者：
M. Hollstein;L. Peri;A. Mandard;J. Welsh;R. Montesano;R. Metcalf;M. Bak;Curtis C. Harris
对居住在乌拉圭和法国诺曼底（酒精饮料和烟草烟雾是主要危险因素）患者的食管鳞状细胞癌 (ESC) 样本进行了 p53 肿瘤抑制基因的点突变分析。通过外显子 5-8 的聚合酶链式反应扩增和直接 DNA 测序，在 34 个肿瘤（15 个来自诺曼底，19 个来自乌拉圭）中鉴定出 p53 基因中导致氨基酸取代或链终止的 15 个点突变。 ESC 中来自这些高发生区域的碱基替换分散在 p53 基因的中部区域。 ESC 与其他类型的胃肠癌之间的差异在于频繁碱基替换的性质。 CpG 到 TpG 的转换在这些 ESC 中远不如在结直肠肿瘤中普遍，而在结肠癌中很少发现的 G 到 T 转换却在四分之一的 ESC 样本中发现。与大多数其他类型实体瘤的突变模式相比，A:T 对的碱基替换构成了 ESC p53 突变的重要组成部分。与这些样本中p53基因的频繁突变相反，通过对已知发生转化突变的外显子进行直接测序，在来自乌拉圭的16个肿瘤中没有发现H-、K-或N-ras基因突变。之前一项关于法国 ESC ras 突变的研究也呈阴性（M. C. Hollstein 等人，Cancer Res., 48: 5119-5123, 1988）。考虑了不同病因在产生这些差异中的作用，以及将患者暴露史与高危人群中 p53 突变模式联系起来的可能性。
Esophageal squamous cell carcinoma (ESC) samples from patients residing in Uruguay and in Normandy, France, where alcoholic beverages and tobacco smoke are major risk factors, were analyzed for point mutations in the p53 tumor suppressor gene. Among 34 tumors (15 from Normandy and 19 from Uruguay) 15 point mutations in the p53 gene that result in amino acid substitutions or chain termination were identified by polymerase chain reaction amplification of exons 5-8 and direct DNA sequencing. Base substitutions in ESC from these high-incidence areas are dispersed over the midregion of the p53 gene. There are differences between ESC and other types of gastrointestinal cancer in the nature of frequent base substitutions. CpG to TpG transitions were far less prevalent in these ESC than in colorectal tumors, whereas G to T transversions, rarely found in colon cancers, were found in one-fourth of the ESC samples. Base substitutions at A:T pairs constitute an important fraction of ESC p53 mutations, in contrast to mutation patterns in most other types of solid tumors. In contrast to the frequent mutation of the p53 gene in these samples, no mutations in the H-, K-, or N-ras genes were found in 16 tumors from Uruguay by direct sequencing of exons in which transforming mutations are known to occur. A previous study on ras mutations in ESC from France was also negative (M. C. Hollstein et al., Cancer Res., 48: 5119-5123, 1988). The role of distinct etiological factors in generating these differences and the potential for linking patient exposure histories with patterns of p53 mutations in high risk populations are considered.