Enomoto T, Fujita M, Inoue M, Nomura T, Shroyer K R
Department of Radiation Biology, Osaka University Faculty of Medicine, Japan.
Am J Clin Pathol. 1995 Feb;103(2):224-30. doi: 10.1093/ajcp/103.2.224.
The authors previously reported a significant frequency of activating point mutations in codon 12 and 13 of the K-ras gene in endometrial carcinoma and endometrial atypical hyperplasia from Osaka, Japan. They also showed that alterations of the p53 gene are found frequently in those tumors. This study was designed to reveal possible demographic differences in the prevalence of K-ras and p53 mutations in endometrial carcinoma. Tumor-enriched areas of paraffin-embedded histologic sections obtained through the Colorado Central Cancer Registry were isolated and extracted for DNA. Fragments amplified by polymerase chain reaction (PCR) were screened for transforming mutations in codon 12, 13, or 59-63 of K-ras by direct sequencing. Of 38 endometrial adenocarcinomas that were analyzed, K-ras activation was detected in 4 cases (11%), three in codon 12 (a single case with a GGT-->AGT transition, a single case with a GGT-->GAT transition, and a single case with a GGT-->TGT transversion) and one in codon 13 (a GGC-->GAC mutation). The prevalence of K-ras mutations was significantly lower in endometrial carcinomas from Colorado (4 of 38, 11%) than in those from Osaka, Japan (17 of 57, 31%; P = .02). Mutations in exons 5-8 of p53 were screened by PCR-SSCP analysis, and subsequently confirmed by direct sequencing. Mutations in the p53 gene were detected in 5 of 38 endometrial carcinomas from Colorado (13%), including a single base substitution mutation in 3 cases (60%) and a deletion mutation in 2 cases (40%). Mutations in the p53 gene were significantly more frequently found in G3 cancers (3 of 7, 43%) than G1-G2 cancers combined (2 of 31, 6%; P = .025). Although the prevalence of p53 mutations in endometrial carcinomas from Colorado was not significantly different compared to that from Osaka, Japan (9 of 40, 23%), a G:C-->A:T transition at a CpG site, which was the most common base substitution mutation among Japanese, was not included in any tumors from Colorado. A rare polymorphism in codon 213 (CGA-->CGG) was observed in three cases. These observations may indicate that genetic or environmental factors may significantly influence the pathway of endometrial carcinogenesis.
作者之前报道，在来自日本大阪的子宫内膜癌和子宫内膜非典型增生中，K-ras基因第12和13密码子的激活点突变频率很高。他们还表明，在这些肿瘤中经常发现p53基因的改变。本研究旨在揭示子宫内膜癌中K-ras和p53突变发生率可能存在的人口统计学差异。通过科罗拉多中央癌症登记处获得石蜡包埋组织切片的肿瘤富集区域，分离并提取DNA。通过聚合酶链反应（PCR）扩增的片段通过直接测序筛选K-ras第12、13或59 - 63密码子的转化突变。在分析的38例子宫内膜腺癌中，4例（11%）检测到K-ras激活，3例在第12密码子（1例GGT→AGT转换，1例GGT→GAT转换，1例GGT→TGT颠换），1例在第13密码子（GGC→GAC突变）。科罗拉多州子宫内膜癌中K-ras突变的发生率（38例中的4例，11%）显著低于日本大阪的子宫内膜癌（57例中的17例，31%；P = 0.02）。通过PCR-SSCP分析筛选p53基因第5 - 8外显子的突变，随后通过直接测序进行确认。在科罗拉多州的38例子宫内膜癌中，5例（13%）检测到p53基因的突变，包括3例（60%）单碱基替换突变和2例（40%）缺失突变。p53基因的突变在G3级癌症（7例中的3例，43%）中比G1 - G2级癌症合并组（31例中的2例，6%）更常见（P = 0.025）。虽然科罗拉多州子宫内膜癌中p53突变的发生率与日本大阪的相比没有显著差异（40例中的9例，23%），但日本最常见的碱基替换突变——CpG位点的G:C→A:T转换，在科罗拉多州的任何肿瘤中均未出现。在3例中观察到密码子213处罕见的多态性（CGA→CGG）。这些观察结果可能表明遗传或环境因素可能显著影响子宫内膜癌发生的途径。
