Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis -: Relationship to disease stage, tumor size, and cirrhosis

被引:246
作者
Wong, N
Lai, P
Lee, SW
Fan, S
Pang, E
Liew, CT
Zhong, S
Lau, JWY
Johnson, PJ
机构
[1] Chinese Univ Hong Kong, Sir Y K Pao Ctr Canc, Dept Clin Oncol, Shatin, Peoples R China
[2] Chinese Univ Hong Kong, Sir Y K Pao Ctr Canc, Dept Surg, Shatin, Peoples R China
[3] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Shatin, Peoples R China
关键词
D O I
10.1016/S0002-9440(10)65248-0
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
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页码:37 / 43
页数:7
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