Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH
Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH
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DOI：
10.1038/modpathol.3800107
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发表时间：
2004-06-01
期刊：
影响因子：
7.5
通讯作者：
Sasaki, K
中科院分区：
文献类型：
--
作者：
Hashimoto, K;Mori, N;Sasaki, K
为了阐明与丙型肝炎病毒相关性肝细胞癌发生发展有关的遗传异常，我们研究了19例经常规和阵列CGH手术切除的肝细胞癌的DNA拷贝数异常(DCNA)。常规CGH显示DNA拷贝数在1q(79%)、8q(37%)、6p(32%)和10p(32%)时频繁增加，17p(79%)、16q(58%)、4q(53%)、13q(42%)、10q(37%)、1p(32%)和8p(32%)DNA拷贝数减少。通常，阵列CGH显示DCNA的基因通常位于染色体区域，而常规CGH分析检测到的DCNA。LAMC2、TGFB2和AKT3基因的拷贝数(位于1q)增加，FGR/SRC2和CyLD基因的拷贝数(分别位于1p和16q)减少，超过30%的肿瘤包括小的、高分化的癌。这些发现表明，这些基因与丙型肝炎-肝细胞癌的发生有关。MOS、MYC、EXT1和PTK2(位于8q上)的增加仅在中、低分化肿瘤中检测到，提示这些改变有助于肿瘤的进展。总之，染色体和阵列CGH技术可以识别与丙型肝炎病毒-肝癌的发展和进展有关的基因。
To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%),16q (58%), 4q (53%),13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1 p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.