Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH

Abstract

To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays

“…Our results indicated that GIM can detect the allelic status more accurately than methods used previously (Kusano et al, 1999;Niketeghad et al, 2001). For example, several HCC samples analysed in the present study had UPD or UPT, which may be missed or recognized as gain regions by CGH, as both CGH and array-based CGH can only detect total copy changes (Hashimoto et al, 2004;Katoh et al, 2005;Patil et al, 2005). Uniparental disomy or UPT are exceptional derivations of a pair of offspring chromosomes from one parent only (Engel, 1980) and cause an increased risk of recessive disorders, such as Wiedemann-Beckwith (Henry et al, 1991), Prader-Willi (Nicholls et al, 1989) and Angelman syndromes (Malcolm et al, 1991) owing to reduction to homozygosity (Engel, 1993).…”

New genetic associations detected in a host response study to hepatitis B vaccine

“…31 Its function on neoplasia during hepatocellular carcinoma remains contentious, but a recent paper has reported an increase in DNA copy number of TGFB2 in hepatocellular carcinoma infected with hepatitis C virus. 32 We have found that three genes outside of the MHC region, TNFSF15, C5 and CCL15, harbor more than one significantly associated polymorphism (Table 2). Linkage disequilibrium among SNPs in two of these genes is high in our population, TNFSF15, r 2 ¼ 0.95 (Supplementary Figure S2) and C5, r 2 ¼ 0.88 (Supplementary Figure S3).…”

Y chromosome loss and other genomic alterations in hepatocellular carcinoma cell lines analyzed by CGH and CGH array

“…Previously reported chromosomal studies on primary HCC tissues and HCC cell lines have suggested that the frequent structural abnormality at 1q is involved in HCC [15,16,26,27]. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes at 1q have been reported in 19 HCC tissues by CGH array [28]. Gains of chromosome 7 are also a recurrent aberration.…”