Chromosomal Aberrations in Korean Hepatocellular Carcinomas

Park, Hwon Kyum; Choi, Dongho; Kim, Han Joon; Lee, Kyeong Geun; Cho, Youl Hee; Lee, Kwang Soo

Abstract

BACKGROUND/AIMS: The pattern of chromosomal gains and losses in HCC with hepatitis B in Korean patients is very complex and involves virtually every site in the genome. This study was done to know the chromosomal aberrations in hepatocellular carcinoma with HBV and relationship between these lesions and previously known oncogenes and tumor suppressor genes.
METHODS
DNA changes in 23 hepatocellular carcinomas (HCC) associated with hepatitis B virus (HBV) were analyzed by CGH technique.
RESULTS
Eighteen of the 23 cases showed genetic alterations. The remaining 5 cases showed no detectable aberrations. The losses of chromosome regions 17p (74%), 4q (57%), 16p (52%), 16q (48%), 8p (43%) and 13q (43%) were detected in the order of decreasing frequency. In cases of multiple losses of chromosomes, a combination of 17p, 16p, 16q, 4q, and 8p losses was found in 5 cases (30%). On the other hand, chromosomal gains occurred on 1q (65%), 8q (52%), 20p (48%) and 20q (43%) in the order of decreasing frequency. And the simultaneous genomic gains of these 4 chromosomes were found in 9 cases (40%). Moreover, the combination of 5 genomic losses (17p, 16p, 16q, 4q, & 8p) and 4 genomic gains (1q, 8q, 20p, & 20q) was observed in 4 cases (23%).
CONCLUSIONS
The pattern of chromosomal gains and losses in HCC with hepatitis B in Korean patients is very complex and involves virtually every site in the genome. This indicates a high genomic instability. This could possibly be explained either as the result of random chromosomal changes during early development of tumor, or as the highly variable and random pattern of integration of HBV in the HCC. The hepatocarcinogenesis may be the result of cumulative effects rather than those orders of occurrence of those genomic changes. The sites of cellular DNA at which HBV integrates frequently undergo rearrangements, resulting in translocations, inverted duplications, deletions, and possibly recombinational events. But, CGH only detects changes of chromosomal copy number but could not identify translocations, inversions, and other aberrations of chromosome. The chromosomal analysis of HCC with HBV in Korean patients by CGH technique confirms the presence of complex and sporadic, but nonrandom genetic changes in the chromosome. In the future, more detailed oncogenic study could be carried out on the chromosomes which showed abnormal aberrations through this study.