Alterations in exon 4 of the p53 gene in gastric carcinoma.
Alterations in exon 4 of the p53 gene in gastric carcinoma.
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DOI：
10.1016/s0016-5085(00)70356-8
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发表时间：
2000-06
期刊：
影响因子：
29.4
通讯作者：
T. Shepherd;D. Tolbert;J. Benedetti;J. Macdonald;G. Stemmermann;J. Wiest;G. Devoe;M. Miller;J. Wang;A. Noffsinger;C. Fenoglio-Preiser
中科院分区：
文献类型：
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作者：
T. Shepherd;D. Tolbert;J. Benedetti;J. Macdonald;G. Stemmermann;J. Wiest;G. Devoe;M. Miller;J. Wang;A. Noffsinger;C. Fenoglio-Preiser
背景与目标我们的长期目标是评估 p53 在胃癌预后中的作用。我们之前仅检查外显子 5-9 时发现 p53 表达与突变存在之间存在差异。然后我们评估了外显子 4。方法对 217 例胃癌进行 DNA 测序，以检测外显子 4 的改变。通过限制酶消化检查密码子72。结果3.2%的肿瘤中存在突变。此外，在密码子36和72处发现了2个多态性位点。密码子36处的多态性仅在2名患者中发现。相比之下，密码子72多态性非常频繁。基因型频率为arg/arg (54%)、arg/pro (33%) 和pro/pro (14%)。多态性位点的基因型因种族而异（P = 0.001）：64% 的白人具有 arg/arg 基因型，而黑人的这一比例为 24%。不同部位、性别或组织学肿瘤类型的基因型差异无统计学意义（P=0.067）。结论胃癌中存在多个外显子4改变。其中包括罕见突变和非常罕见的密码子 36 多态性。最常见的变化是密码子72多态性，其基因型因种族而存在显着差异。白人中更常见的 arg/arg 基因型可以解释为什么白人更容易患贲门癌，而黑人中更常见的脯氨酸等位基因可以解释为什么他们更容易患胃窦癌。需要进一步的研究来确定密码子 72 多态性是否影响患者患胃癌的倾向。胃肠病学 2000;118:1039-1044
Background & AimsOur long-term goal was to evaluate the role of p53 in the prognosis of gastric cancer. We previously showed a discrepancy between p53 expression and the presence of mutations when only exons 5-9 were examined. We then evaluated exon 4.MethodsDNA was sequenced from 217 gastric cancers to detect exon 4 alterations. Codon 72 was examined by restriction enzyme digestion.ResultsMutations were present in 3.2% of tumors. In addition, 2 polymorphic sites were found at codons 36 and 72. Polymorphisms at codon 36 were only found in 2 patients. In contrast, the codon 72 polymorphism was very frequent. The genotype frequency was arg/arg (54%), arg/pro (33%), and pro/pro (14%). The genotype of the polymorphic site varied with race (P = 0.001): 64% of whites had the arg/arg genotype, compared with 24% of blacks. The difference in genotype by site, sex, or histological tumor type was not statistically significant (P = 0.067).ConclusionsThere are several exon 4 alterations in gastric cancers. These include the rare mutations and the very rare codon 36 polymorphism. The most common change is the codon 72 polymorphism, the genotype of which differs significantly with race. The more common arg/arg genotype in whites may explain why whites are more prone to develop cardiac cancer, whereas the more common proline allele in blacks may explain why they are more prone to develop antral cancers. Further studies are required to determine whether the codon 72 polymorphism affects patient predisposition to gastric cancer. GASTROENTEROLOGY 2000;118:1039-1044