Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis -: Relationship to disease stage, tumor size, and cirrhosis
Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis -: Relationship to disease stage, tumor size, and cirrhosis
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DOI：
10.1016/s0002-9440(10)65248-0
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发表时间：
1999-01-01
影响因子：
6
通讯作者：
Johnson, PJ
中科院分区：
文献类型：
--
作者：
Wong, N;Lai, P;Johnson, PJ
肝细胞癌（I-ICC）是一种常见的高度恶性肿瘤，在东南亚流行。虽然相关的病因学因素现在已经得到了很好的认识，但个体因素之间的相互作用以及它们导致癌症的分子机制仍然不清楚。由于肝细胞在体外生长不良，对HCC的细胞遗传学分析受到限制。然而，最近开发的比较基因组杂交（CGH）技术，允许筛选整个基因组，而不需要细胞培养。应用CGH技术对67例HCC、3例腺瘤样增生（AH）和12例癌旁非肿瘤性肝硬化的手术切除标本进行了基因组畸变研究。所有样本均来自中国南方种族和病原学同质人群的患者，慢性B型肝炎病毒感染是主要病因。HCC样本的CGH分析显示Iq的拷贝数增加频繁（48/67例，72%），8q（32/67例，48%），174（20/67例，30%），20 q 4q（29/67例，43%）、8p（25/67例，37%）、13q（25/67例，37%）和16q（20/67例，30%）的常见丢失。我们发现高发病率的Iq增益强烈建议这种畸变与肝癌的发展。在3例AH标本中的1例中检测到基因组异常，但在所有12例肿瘤周围的组织中均未检测到基因组异常。临床分期T1期3例，T2期53例，T3期11例，T2期与T3期之间基因组失衡模式无显著性差异，但直径大于3cm的肝癌中4q11-q25拷贝数丢失明显，特别令人感兴趣的是，在所有12例发生于非炎性肝脏的HCC病例中鉴定出8q拷贝数增加，而在55例发生于炎性肝脏的HCC病例中仅鉴定出20例。我们认为，8q的过度表达可能与生长优势和增殖刺激有关，这些刺激促进了非恶性肿瘤人肝脏的恶性变化。
Hepatocellular carcinoma (I-ICC) is a common and highly malignant tumor that is prevalent in Southeast Asia. Although the etiological factors associated are now well recognized, the interactions between individual factors and the molecular mechanisms by which they lead to cancer remain unclear. Cytogenetic analysis on HCC has been Limited because of poor hepatocyte growth in vitro. The recently developed technique of comparative genomic hybridization (CGH), however, permits screening of the entire genome without the need of cell culture. CGH was applied to the study of genomic aberrations in 67 surgically resected samples of HCC, 3 of adenomatous hyperplasia (AH), and 12 of nontumorous cirrhotic liver surrounding the tumors. All samples were from patients of a racially and etiologically homogeneous population in Southern China, where chronic hepatitis B virus infection is the main etiological factor. CGH analysis of the HCC samples revealed frequent copy number gain of Iq (48/67 cases, 72%), 8q (32/67 cases, 48%), 174 (20/67 cases, 30%), and 20q (25/67 cases, 37%) and common losses on 4q (29/67 cases, 43%), 8p (25/67 cases, 37%), 13q (25/67 cases, 37%), and 16q (20/67 cases, 30%). Our finding of a high incidence of Iq gain strongly suggested this aberration was associated with the development of HCC. Genomic abnormalities were detected in 1 of the 3 AH specimens but absent in all 12 cirrhotic tissues surrounding the tumor. Clinical staging classified 3/67 HCC cases as T1, 53 cases as T2, and 11 cases as T3, No significant difference in the pattern of genomic imbalances was detected between stages T2 and T3, A significant copy number loss of 4q11-q25 was, however, identified in those tumors larger than 3 cm in diameter, Of particular interest was the identification of 8q copy number gain in all 12 cases of HCC that arose in a noncirrhotic liver, compared with only 20/55 cases in HCC arising in a cirrhotic Liver. We suggest that 8q over-representation is likely associated with a growth advantage and proliferative stimulation that have encouraged malignant changes in the noncirrhotic human liver.