Hepatitis B virus-associated hepatocellular carcinoma from India: role of viral genotype and mutations in CTNNB1 (beta-catenin) and TP53 genes.
OBJECTIVE
Chronic hepatitis B virus (HBV) infection is the major risk factor for hepatocellular carcinoma (HCC) in India. Studies from other countries have linked HBV genotype C to a higher risk for HCC. This study was carried out to determine the association between genotype and HCC and also the frequency of mutations in CTNNB1 (beta-catenin) and TP53 genes in HBV-related HCC.


METHODS
Formalin-fixed paraffin-embedded (FFPE) tissues from 20 (15 autopsy, five resected specimens) cases of HBV-associated HCC were examined. Viral genotype was determined by sequencing portions of the HBV S gene using four overlapping PCR amplicons. Exon 3 of CTNNB1 and exon 7 of TP53 were sequenced.


RESULTS
HBV genotyping was possible in 14 of 20 cases; genotype D was most common (n = 11) followed by C (n = 2) and A (n = 1). CTNNB1 mutations were noted in two of 15 amplifiable cases while two of 10 specimens showed TP53 mutations.


CONCLUSIONS
HBV genotype can be ascertained from FFPE sections by sequencing multiple overlapping fragments to avoid the limitation of fragmented DNA. Genotype D was the common genotype in HBV-associated HCC. The very low frequency of TP53 mutation suggests low levels of aflatoxin B₁ exposure. The beta-catenin pathway appears not to be significantly involved in HBV-related HCC in India. However, further larger studies are required to confirm these findings.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Perumal
P
Vivekanandan
Michael
M
Torbenson
Banumathi
B
Ramakrishna
D000328:Adult; D000368:Aged; D001344:Autopsy; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007194:India; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
C495270:CTNNB1 protein, human; D004279:DNA, Viral; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin