Baffa R, Negrini M, Mandes B, Rugge M, Ranzani G N, Hirohashi S, Croce C M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Cancer Res. 1996 Jan 15;56(2):268-72.
Loss of heterozygosity (LOH) at several chromosomal loci is a common feature of the malignant progression of human tumors. In the case of chromosome 11, LOH has been well documented in several types of solid neoplasms, including gastric carcinoma, suggesting the presence of suppressor gene(s) at 11p15 and 11q22-23. Little is currently known about the molecular events occurring during the development of gastric cancer. To define the regions of chromosome 11 involved in gastric cancer progression, we used high-density polymorphic markers to screen for LOH in matched normal and tumor tissue DNA from 60 primary gastric carcinomas. We found that 21% of the tumors showed LOH simultaneously at 11p15 and 11q22-23, 41% had LOH at 11p15, and 30% had LOH at 11q22-23. We confirm that the minimal critical area of LOH for 11p15.5 is the approximately 2-Mb region between loci D11S1318 and D11S988. However, when we analyzed the pattern of LOH according to the country of origin of the patient, LOH for 11q22-23 alone was found only in cases from Italy. The minimal critical region of LOH at 11q22-23 is identical to that identified for other solid tumors, suggesting that the same putative tumor suppressor gene(s) contained within this region is involved in the pathogenesis of several common human tumors.
几个染色体位点的杂合性缺失（LOH）是人类肿瘤恶性进展的一个常见特征。在11号染色体的情况下，LOH在包括胃癌在内的几种实体瘤中已有充分记录，这表明在11p15和11q22 - 23存在抑癌基因。目前对胃癌发生过程中发生的分子事件知之甚少。为了确定11号染色体上参与胃癌进展的区域，我们使用高密度多态性标记物对60例原发性胃癌的配对正常组织和肿瘤组织DNA进行LOH筛查。我们发现，21%的肿瘤在11p15和11q22 - 23同时出现LOH，41%在11p15有LOH，30%在11q22 - 23有LOH。我们证实，11p15.5的LOH最小关键区域是位点D11S1318和D11S988之间约2 Mb的区域。然而，当我们根据患者的原籍国分析LOH模式时，仅在来自意大利的病例中发现了11q22 - 23单独的LOH。11q22 - 23的LOH最小关键区域与其他实体瘤中确定的区域相同，这表明该区域内包含的相同假定抑癌基因参与了几种常见人类肿瘤的发病机制。
