Marked genetic similarities between hepatitis B virus-positive and hepatitis C virus-positive hepatocellular carcinomas

Abstract

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Well-established risk factors include infections with two very different viruses: the DNA virus causing hepatitis B (HBV) and the RNA virus inducing hepatitis C (HCV). In order to determine whether genetic differences exist between HBV- and HCV-induced HCC, 41 HCC samples of known vival status were examined by comparative genomic hybridization (CGH). The analysis revealed frequent deletions of 1p (24%), 4q (39%), 6q (41%), 8p (44%), 9p (24%), 11q (24%), 12q (22%), and 13q (39%), as well as common gains of 1q (46%), 6p+ (20%), 8q+ (41%), 11q (27%), and 17q+ (37%). There was no significant difference in the number and type of chromosomal imbalances between 25 HCV- and 16 HBV-infected tumours. This is consistent with models suggesting that HBV and HCV cause cancer through non-specific inflammatory and regenerative processes, rather than through virus-specific interactions with defined target genes. Chromosomal imbalances were also unrelated to the grade and stage of HCC. This may suggest that most gross genomic alterations occur early during HCC development and that further progression of these tumours may be associated with other types of genetic changes, not detectable by CGH. In summary, these data show that characteristic gross genomic changes occur in HCC, but these alterations at present do not appear to have diagnostic or prognostic applications.

Different genomic imbalances in low- and high-grade HCV-related lymphomas

“…In three cases, 2q loss was associated with 1q gain, which has been also found in HCV-related hepatocellular carcinomas. 6 In two of our patients with 2q loss, LBCL was derived from low-grade lymphoma. This progression has previously been observed in MALT-type MZL associated with H. pylori infection.…”

p53 immunocytochemistry and TP53 gene mutations in patients with chronic hepatitis C virus (HCV) infection.

“…In HCC described by European authors mutation in the codon 249 was detected in a single case [19]. Few studies have suggested that losses and gains of chromosome regions may differ in HCCs caused by HBV as compared to HCV infection [39]. Few studies have dealt with incidence of genetic aberrations in TP53 in patients with non-neoplastic liver pathology or with risk factors prompting development of HCC (e.g.…”

Identification, using cDNA macroarray analysis, of distinct gene expression profiles associated with pathological and virological features of hepatocellular carcinoma

“…HBV-and HCV-related HCC. Dierent studies have led to report that a number of genetic alteration are common to HCV-and HBV-related HCCs (Buendia, 2000;Honda et al, 2001;Kusano et al, 1999;LaurentPuig et al, 2001;Tornillo et al, 2000). Our study adds further support to the hypothesis that liver carcinogenesis induced by HBV and HCV may, in addition to common genetic and epigenetic alterations, involve distinct pathways.…”

“…A number of genetic alterations have been described in several HCC related to HCV or HBV (Buendia, 2000;Kusano et al, 1999;Tornillo et al, 2000). Various carcinogenetic mechanisms have been described in HBV-related HCC (Brechot et al, 2000).…”

“…There is evidence for an association between certain chromosomal alterations and the HBV or HCV status of HCC, but the molecular basis of these observations remains unclear (Buendia, 2000;Tornillo et al, 2000). Furthermore, apart from the determination of alpha-fetoprotein serum levels, currently used for the diagnosis of HCC, we still lack reliable markers for early tumour detection (Pateron et al, 1994).…”