Allelic imbalance regions on chromosomes 8p, 17p and 19p related to metastasis of hepatocellular carcinoma: comparison between matched primary and metastatic lesions in 22 patients by genome-wide microsatellite analysis
Allelic imbalance regions on chromosomes 8p, 17p and 19p related to metastasis of hepatocellular carcinoma: comparison between matched primary and metastatic lesions in 22 patients by genome-wide microsatellite analysis
复制标题
DOI：
10.1007/s00432-002-0407-5
复制
发表时间：
2003-05
影响因子：
3.6
通讯作者：
Lianda Zhang;L. Qin;Zeng-chen Ma;S. Ye;Yin‐kun Liu;Q. Ye;Xin Wu;Wei Huang;Zhao-You Tang
中科院分区：
文献类型：
--
作者：
Lianda Zhang;L. Qin;Zeng-chen Ma;S. Ye;Yin‐kun Liu;Q. Ye;Xin Wu;Wei Huang;Zhao-You Tang
为了了解肝细胞癌（HCC）转移的分子机制，有必要确定其进展过程中积累的遗传改变以及癌细胞中获得转移潜力的遗传改变。在我们之前的研究中，使用比较基因组杂交（CGH），我们发现8p染色体的丢失在转移性病变中比在匹配的原发性肝癌肿瘤中更常见。因此，8p缺失可能与HCC转移有关。为了缩小转移相关改变区域的范围，我们通过全基因组微卫星分析分析了22例原发性和匹配的HCC转移灶。在17p、8p11-cen、8p21- 23,4q32 -qter、4q13- 23,16q和1p33上发现了高水平等位基因失衡（AI）的共同区域。转移灶中AI升高的区域为8p23.3、8p11.2、17p11.2-13.3、4q21-22、4q32-qter、8q24.1、9p11、9q31、11q23.1、13q14.1- 31,13q32 -qter、16p13.3、16q13、16q22、19p13.1，认为与转移表型有关。其中，8p的缺失再次被证实与HCC的进展和转移有关，8p23.3和8p11.2是两个可能存在转移相关基因的区域。在HCC中也首次发现19p13.1的AI也可能与转移潜能有关。这些结果为进一步研究肝癌转移抑制基因提供了一些候选区域。
To understand the molecular mechanisms of metastasis in hepatocellular carcinoma (HCC), it is necessary to identify the accumulating genetic alterations during its progression as well as those responsible for the acquisition of metastatic potential in cancer cells. In our previous study, using comparative genomic hybridization (CGH), we found that loss on chromosome 8p is more frequent in metastatic lesions than in matched primary tumors of HCC. Thus, 8p deletion might contribute to HCC metastasis. To narrow the location of metastasis-related alteration regions, we analyzed 22 primary and matched metastatic lesions of HCC by genome-wide microsatellite analysis. Common regions with high levels of allelic imbalance (AI) were identified on 17p, 8p11-cen, 8p21-23, 4q32-qter, 4q13-23, 16q, and 1p33. Regions with increased AI in metastatic lesions were 8p23.3, 8p11.2, 17p11.2-13.3, 4q21-22, 4q32-qter, 8q24.1, 9p11, 9q31, 11q23.1, 13q14.1-31, 13q32-qter, 16p13.3, 16q13, 16q22, and 19p13.1, and these were considered to be related to the metastasis phenotype. Among them, loss on 8p was again proved to be related to progression and metastasis of HCC, and 8p23.3 and 8p11.2 were two likely regions harboring metastasis-related genes. It was also shown for the first time in HCC that AI of 19p13.1 might also be related to metastatic potential. These results provide some candidate regions for further study to identify putative genes suppressing metastasis of HCC.