Semba S, Yokozaki H, Yasui W, Tahara E
First Department of Pathology, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan.
Int J Oncol. 1998 Jun;12(6):1245-51. doi: 10.3892/ijo.12.6.1245.
It is known that nearly 5% of gastric carcinomas arise under the age of 40. To elucidate genetic alterations in these patients, we performed studies using microsatellite assay in 27 gastric cancers under 35 years of age, composed of 5 well and 22 poorly differentiated adenocarcinomas. We detected replication errors (RERs) in 18 (67%) of 27 tumors, but no germline mutation in DNA mismatch repair genes (hMLH1 and hMSH2), except fory 3 somatic mutations in the hMLH1 gene. Loss of heterozygosity (LOH) at D17S855, located on chromosome 17q21 (BRCA1), was detected in 8 (40%) of 20 informative cases. In 12 (44%) of 27 cases, LOH on chromosome 17q12-21 including the BRCA1 was found in several neighboring markers in this region, while no mutation was found in the BRCA1 gene. Four (40%) of 10 scirrhous type gastric cancers exhibited wide allelic deletions on chromosome 17q12-21. These results overall suggest that young gastric cancer patients display highly frequent micro-satellite instability that might be due to defect of DNA repair system rather than hMLH1 and hMSH2. In addition, chromosome 17q12-21 including BRCA1 locus may contain a candidate for tumor suppressor gene, particularly in scirrhous type gastric cancers arising in young patients.
已知近5%的胃癌发生在40岁以下。为了阐明这些患者的基因改变，我们对27例35岁以下的胃癌进行了微卫星分析研究，其中包括5例高分化和22例低分化腺癌。我们在27例肿瘤中的18例（67%）检测到复制错误（RERs），但在DNA错配修复基因（hMLH1和hMSH2）中未检测到种系突变，仅在hMLH1基因中发现3例体细胞突变。在20例信息充分的病例中，有8例（40%）检测到位于17号染色体q21（BRCA1）上的D17S855杂合性缺失（LOH）。在27例病例中的12例（44%）中，在该区域的几个相邻标记中发现了包括BRCA1在内的17号染色体q12 - 21上的LOH，而在BRCA1基因中未发现突变。10例硬癌型胃癌中有4例（40%）在17号染色体q12 - 21上表现出广泛的等位基因缺失。这些结果总体表明，年轻胃癌患者表现出高度频繁的微卫星不稳定性，这可能是由于DNA修复系统缺陷而非hMLH1和hMSH2所致。此外，包括BRCA1位点在内的17号染色体q12 - 21可能包含一个肿瘤抑制基因候选者，特别是在年轻患者发生的硬癌型胃癌中。
