Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis
Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis
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DOI：
10.1053/gast.2001.24798
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发表时间：
2001-06-01
期刊：
影响因子：
29.4
通讯作者：
Zucman-Rossi, J
中科院分区：
文献类型：
--
作者：
Laurent-Puig, P;Legoix, P;Zucman-Rossi, J
背景与目的：为了评估遗传改变的特征如何有助于阐明肝癌发生途径，分析了137个肿瘤。（方法）在bar下：检测高密度等位基因型、p53、Axin 1和β-catenin基因突变。根据临床参数分析变化。（结果）bar下：根据染色体的稳定性，肿瘤可分为2组。在第一组中，证明了染色体稳定性，与染色体8 p丢失相关的β-连环蛋白突变经常被发现为单个遗传改变。β-连环蛋白突变与大肿瘤大小和阴性B型肝炎病毒状态相关。在第二组中，表现出染色体不稳定性，最常见的等位基因丢失位于染色体1 p、4 q、60、9 p、13 q、16 p、16 q和17 p上; Axin 1和p53经常突变。除了6 q和9 p缺失外，所有这些改变都与B病毒感染有关，P53突变、17 p、13 q缺失和高分数等位基因缺失指数与低分化肿瘤有关，与危险因素无关。最后，在整个系列中，染色体9 p和6 q缺失与预后不良有关。（结论）bar下：两种主要的遗传学改变所定义的通路显示出不同的危险因素和临床特征。此外，染色体9 p或6 q的丢失是一个独立的预后指标。
(Background & Aims) under bar: To evaluate how characterization of genetic alterations can help in the elucidation of liver carcinogenesis pathways, 137 tumors were analyzed. (Methods) under bar: High-density allelotype, p53, Axin1, and beta -catenin gene mutations were determined. Alterations were analyzed according to clinical parameters. (Results) under bar: Tumors could be divided into 2 groups according to chromosome stability status. In the first group, demonstrating a chromosome stability, beta -catenin mutation associated with chromosome 8p losses were frequently found as the single genetic alterations. beta -catenin mutations were associated with large tumor size and with negative hepatitis B virus status. In the second group, demonstrating a chromosome instability, the most frequent allelic losses were on chromosome 1p, 4q, 60, 9p, 13q, 16p, 16q, and 17p; Axin1 and p53 were frequently mutated. All of these alterations, except losses on 6q and 9p, were associated with hepatitis B virus infection, P53 mutations, 17p, 13q losses, and a high value of the fractional allelic loss index were associated with poor differentiated tumors, independently of risk factors, Finally, in the whole series, chromosome 9p and 6q losses were associated with poor prognosis, (Conclusions) under bar: Two main pathways defined by genetic alterations show different risk factors and clinical characteristics. Furthermore, loss of chromosome 9p or 6q is an independent prognostic indicator.