Hepatitis B virus-associated hepatocellular carcinoma from India: role of viral genotype and mutations in CTNNB1 (beta-catenin) and TP53 genes.
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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DOI：
10.1007/s12029-010-9222-4
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发表时间：
2011-03
影响因子：
1.6
通讯作者：
Ramakrishna B
中科院分区：
文献类型：
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作者：
Vivekanandan P;Torbenson M;Ramakrishna B
慢性B型肝炎病毒（HBV）感染是印度肝细胞癌（HCC）的主要危险因素。来自其他国家的研究已经将HBV基因型C与HCC的高风险联系起来。本研究旨在确定基因型与HCC之间的关系，以及HBV相关HCC中CTNNB 1（β-连环蛋白）和TP 53基因突变的频率。对20例HBV相关性HCC（15例尸检，5例切除标本）的福尔马林固定石蜡包埋（FFPE）组织进行了检查。通过使用四个重叠PCR扩增子对HBV S基因部分进行测序来确定病毒基因型。对CTNNB 1基因第3外显子和TP 53基因第7外显子进行测序。20例中有14例可能进行HBV基因分型;基因型D最常见（n = 11），其次是C（n = 2）和A（n = 1）。CTNNB 1突变在15例可确诊病例中有2例，而10例标本中有2例显示TP 53突变。通过对多个重叠片段进行测序，可以从FFPE切片中确定HBV基因型，以避免片段化DNA的限制。D基因型是HBV相关性肝癌的常见基因型。TP 53突变的频率非常低，表明黄曲霉毒素B1暴露水平较低。在印度，β-连环蛋白通路似乎与HBV相关的HCC无关。然而，需要进一步的更大规模的研究来证实这些发现。
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. 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. 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. 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.