Frequent rearrangements at minisatellite loci D1S7 (1p33-35), D7S22 (7q36-ter) and D12S11 (12q24.3-ter) in hepatitis B virus-positive hepatocellular carcinomas from Thai patients.

Abstract

Primary hepatocellular carcinoma (HCC) is one of the most common cancers in Thailand; chronic infection with hepatitis B virus (HBV) is endemic and represents a major risk factor for the development of this cancer. Several mechanisms for HBV-related hepatocarcinogenesis have been proposed, among them a direct role of HBV in the promotion of genetic recombination leading to chromosomal alterations. Minisatellite DNA sequences are hypervariable regions dispersed throughout the genome which are susceptible to genetic recombination events. In the present study, somatic rearrangements affecting minisatellite sequences were examined in a total of 26 HCC from Thai patients. Multilocus DNA fingerprinting using probes 33.15 and 33.6 detected rearrangements in 11 and 12 HCC, respectively, all of them carrying integrated HBV DNA. The frequency of rearranged bands was calculated for each probe based on the total number of rearrangements observed in the 26 tumours and the total number of bands revealed by DNA fingerprinting in the non-tumour DNA. With each probe a total of 23 rearrangements was observed, yielding rearrangement frequencies of 3.7% and 4.2% for the 33.15 and 33.6 minisatellite families, respectively. To test for possible clustering of these rearrangements at specific loci, we used minisatellite locus-specific probes previously cloned from 33.15 and 33.6. Minisatellites located at 1p33-35, 7q36-ter and 12q24.3-ter were shown to be frequently affected by rearrangement events in this series of HBV-positive HCC. Frequent rearrangements at minisatellite locus D7S22 (7q36-ter) in HBV-positive human HCC have not been reported so far.