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Hepatitis B Virus-Associated Hepatocellular Carcinoma from India: Role of Viral Genotype and Mutations in CTNNB1 (Beta-Catenin) and TP53 Genes

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Abstract

Purpose

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.

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Acknowledgment

Michael Torbenson was supported by National Institutes of Health grant RO1DK078686.

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Perumal Vivekanandan & Michael Torbenson

  2. Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India, 632004

    Banumathi Ramakrishna

Authors
  1. Perumal Vivekanandan
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  2. Michael Torbenson
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  3. Banumathi Ramakrishna
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Correspondence to Banumathi Ramakrishna.

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Vivekanandan, P., Torbenson, M. & Ramakrishna, B. Hepatitis B Virus-Associated Hepatocellular Carcinoma from India: Role of Viral Genotype and Mutations in CTNNB1 (Beta-Catenin) and TP53 Genes. J Gastrointest Canc 42, 20–25 (2011). https://doi.org/10.1007/s12029-010-9222-4

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