Nagai H, Pineau P, Tiollais P, Buendia M A, Dejean A
Unité de Recombinaison et Expression Génétique, INSERM U163, Institut Pasteur, Paris, France.
Oncogene. 1997 Jun 19;14(24):2927-33. doi: 10.1038/sj.onc.1201136.
Hepatocellular carcinoma (HCC) is one of the most common cancers in many parts of the world, however the molecular mechanisms underlying liver cell transformation remain obscure. A genome-wide scan of loss of heterozygosity (LOH) in tumors provides a powerful tool to search for genes involved in neoplastic processes. To identify recurrent genetic alterations in liver tumors, we examined DNAs isolated from 120 HCCs and their adjacent non tumorous parts for LOH using a collection of 195 microsatellite markers located roughly every 20 cM throughout 39 autosomal arms. The mean heterozygosity was 73%. Our findings provide additional support that LOH for loci on chromosomal arms 1p, 4q, 6q, 8p, 13q and 16p is significantly elevated in HCC. The highest percentage of LOH is found for a locus in 8p23 (42% of informative csaes). This corresponds to one of the most common genetic abnormalities reported to date in these tumors. In addition, high ratio of LOH (> or = 35%) is observed on chromosome arms which had not been implicated in previous studies, notably on 1q, 2q and 9q. No correlation was found between LOH of specific chromosomal regions and etiologic factors such as chronic infections with hepatitis B or C viruses. This first report of an extensive allelotypic analysis of HCC should help in identifying new genes whose loss of function contributes to the development of liver cancer.
肝细胞癌（HCC）是世界许多地区最常见的癌症之一，然而肝细胞转化的分子机制仍不清楚。对肿瘤杂合性缺失（LOH）进行全基因组扫描为寻找参与肿瘤形成过程的基因提供了一个有力工具。为了鉴定肝肿瘤中反复出现的基因改变，我们使用一组195个微卫星标记对从120例HCC及其相邻非肿瘤组织中分离的DNA进行LOH检测，这些标记大致每隔20cM分布于39条常染色体臂上。平均杂合性为73%。我们的研究结果进一步支持了在HCC中，1p、4q、6q、8p、13q和16p染色体臂上基因座的LOH显著升高。在8p23的一个基因座上发现了最高的LOH百分比（42%的信息病例）。这与迄今为止这些肿瘤中报道的最常见基因异常之一相对应。此外，在先前研究中未涉及的染色体臂上观察到高比例的LOH（≥35%），特别是在1q、2q和9q上。未发现特定染色体区域的LOH与病因学因素（如乙型或丙型肝炎病毒慢性感染）之间存在相关性。这篇关于HCC广泛等位基因分析的首次报告应有助于鉴定新的基因，其功能丧失有助于肝癌的发生。
