Choi Y W, Heath E I, Heitmiller R, Forastiere A A, Wu T T
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Mod Pathol. 2000 Oct;13(10):1055-9. doi: 10.1038/modpathol.3880194.
Beta-catenin plays important roles in both intercellular adhesion and signal transduction. Mutations in the beta-catenin or adenomatous polyposis coli (APC) gene can alter the degradation of beta-catenin and cause aberrant accumulation of beta-catenin result in increased transcription of target genes. The dysregulated APC/beta-catenin pathway has been recently discovered as an important mechanism of tumorigenesis in various cancers, but its role in esophageal adenocarcinomas is not clear. Therefore, we studied the beta-catenin gene mutation, allelic loss of chromosome 5q, and APC gene mutation in esophageal and esophagogastric junction adenocarcinomas. Two (2%) somatic mutations in exon 3 of the beta-catenin gene, encompassing the region for glycogen synthase kinase-3beta phosphorylation, were detected from 109 adenocarcinomas. Chromosomal allelic loss on 5q was frequent in 45.3% (44/97) of tumors. Only one missense mutation in the mutation cluster region of the APC gene was detected from 38 esophageal and esophagogastric junction adenocarcinomas with the 5q allelic loss. Our results based on partial screening mutational analyses indicate that mutations of APC/beta-catenin pathway, unlike in colorectal carcinoma, involve only a small subset of esophageal and esophagogastric junction adenocarcinoma.
β-连环蛋白在细胞间黏附和信号转导中均发挥着重要作用。β-连环蛋白或腺瘤性息肉病 coli（APC）基因的突变可改变β-连环蛋白的降解，并导致β-连环蛋白异常蓄积，进而导致靶基因转录增加。最近发现，失调的APC/β-连环蛋白途径是多种癌症发生的重要机制，但其在食管腺癌中的作用尚不清楚。因此，我们研究了食管和食管胃交界腺癌中β-连环蛋白基因突变、5号染色体q臂等位基因缺失以及APC基因突变情况。在109例腺癌中检测到2例（2%）β-连环蛋白基因第3外显子的体细胞突变，该区域包含糖原合酶激酶-3β磷酸化区域。5q染色体等位基因缺失在45.3%（44/97）的肿瘤中较为常见。在38例伴有5q等位基因缺失的食管和食管胃交界腺癌中，仅检测到1例APC基因突变簇区域的错义突变。我们基于部分筛选突变分析的结果表明，与结直肠癌不同，APC/β-连环蛋白途径的突变仅涉及一小部分食管和食管胃交界腺癌。
