SIAHI inactivation correlates with tumor progression in hepatocellular carcinomas
SIAHI inactivation correlates with tumor progression in hepatocellular carcinomas
复制标题
DOI：
10.1002/gcc.10170
复制
发表时间：
2003-03-01
影响因子：
3.7
通讯作者：
Ikai, I
中科院分区：
文献类型：
--
作者：
Matsuo, K;Satoh, S;Ikai, I
16号染色体上的杂合性缺失（洛）在人肝细胞癌（HCC）中经常发生。为了鉴定与肝癌发生有关的肿瘤抑制基因（TSGs），我们对59例肝癌进行了16号染色体的缺失定位。三个常见的缺失区域，位于16q12.1，16q22.1和16q24.2。由于目前尚无关于HCC中16 q12.1位点洛缺失的研究，我们将研究重点放在该区域。通过检索美国国家生物技术信息中心网站上的人类基因组数据库，我们确定了16 q12.1中的14个已知基因作为TSG候选基因。其中，SIAH 1的表达在HCC中显著下调，SIAH 1表达的失活与16 q12.1的洛缺失相关。SIAH 1基因突变分析显示，没有体细胞突变，但一个单核苷酸多态性被发现在35个肝癌调查。随后，我们评估了SIAH 1表达与肝癌临床病理参数之间的关系，并通过半定量RT-PCR证实。SIAH 1在晚期HCC中显著下调，包括低分化肿瘤、较大肿瘤和晚期肿瘤。这些发现表明SIAH 1的失活在HCC进展中起重要作用。(C)2003 Wiley-Liss，Inc.
Accumulation of loss of heterozygosity (LOH) on chromosome 16 is frequently observed in human hepatocellular carcinomas (HCCs). To identify tumor-suppressor genes (TSGs) involved in hepatocarcinogenesis, we performed deletion mapping of chromosome 16 in 59 HCCs. Three commonly deleted regions, located in 16q12.1, 16q22.1, and 16q24.2, were observed. Because there has been no study on LOH at locus l6q12.1 in HCCs, we focused on this region. By searching the Human Genome Database at the National Center for Biotechnology Information web site, we identified 14 known genes in 16q12.1 as TSG candidates. Among these, the expression of SIAH1 was markedly downregulated in HCCs, and inactivation of SIAH1 expression was associated with LOH at 16q12.1. A mutation analysis of SIAH1 revealed no somatic mutations, but one single nucleotide polymorphism was found among the 35 HCCs investigated. Subsequently, we evaluated the relation between SIAH1 expression, confirmed by semiquantitative RT-PCR, and clinicopathological parameters in HCCs. SIAH1 was significantly downregulated in advanced HCCs, including poorly differentiated tumors, larger tumors, and tumors in advanced stages. These findings suggest that inactivation of SIAH1 plays an important role in HCC progression. (C) 2003 Wiley-Liss, Inc.