Regional over-representations on chromosomes 1q, 3q and 7q in the progression of hepatitis B virus-related hepatocellular carcinoma.
Hepatocellular carcinoma is a highly malignant tumor that is prevalent in Southeast Asia and China, where hepatitis B viral infection is the main etiologic factor. Despite a high incidence of hepatocellular carcinoma developing in patients with viral hepatitis B-induced liver cirrhosis, the molecular events underlying the malignant liver progression remain largely unclear. In an effort to characterize the genetic abnormalities involved in the hepatitis B-related liver carcinogenesis, we performed genome-wide explorations by the technique of comparative genomic hybridization (CGH) on 100 hepatocellular carcinoma tumors that arose from hepatitis B-induced liver cirrhosis. According to the American Joint Committee on Cancer staging, four cases were classified as stage I, 69 as stage II, 23 as stage III and four as stage IV. CGH analysis indicated chromosomal instability in both early (stages I/II) and advanced (stages III/IV) stage tumors, with common gains on 1q, 8q and 17q23-q25, and losses on 4q22-q35, 8p21-p22, 13q14-q21, 16q and 17p identified in both groups (P>0.05). Nevertheless, preferential sites of chromosomal defects in relation to hepatocellular carcinoma progression were also identified. Statistical correlations suggested a higher incidence of regional 1q21-q22, 3q22-q28, 7q21-q22 and 7q34-q36 over-representations in association with the advanced stage tumors (P<0.05). In this study, our novel identification of specific chromosomal aberrations in relation to the advanced stage tumors may represent a first step towards mapping genes linked to the progression of hepatocellular carcinoma.
Sy
Shirley M-H
SM
Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, N.T., SAR Hong Kong, China.
Wong
Nathalie
N
Lai
Paul B-S
PB
To
Ka-Fai
KF
Johnson
Philip J
PJ
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006515:Hepatitis B virus; D006526:Hepatitis C / Q000150:complications* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization / Q000379:methods