The pattern of gene copy number variations (CNVs) in hepatocellular carcinoma; in silico analysis

Abstract

Abstract Recent studies showed that genetic lost or gain in the genome can predispose cells toward malignancy. Hepatocellular carcinoma (HCC) is the most common type of liver cancer which occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Prognosis of HCC is strongly connected with diagnostic delay. To date, no ideal screening modality has been developed for HCC. Recent findings demonstrated that Copy number variation (CNVs) can lead to activation of oncogenes and inactivation of tumor suppressor genes in cancers. In this study, CNV profile of 361 HCC samples was evaluated to reveal the potent - chromosomal regions involved in the disease. The obtained data showed that the chr1q and chr8p were two hotspot regions for gene amplifications and deletions in studied samples respectively. In this research, YY1AP1 (Yin Yang-1 Associated Protein 1) on chr1q22 was the most amplified gene in HCC samples and showed the positive correlation with tumor grade. Deletion of CHMP7 (Charged Multivesicular Body Protein 7) on chr8p21.3 was another frequently observed CNV among HCC patients. Both genes were interacted with variety of well-known oncogenes and tumor suppressor genes including YY1 (Yin Yang 1), CCND1 (Cyclin D1), HDAC1 (Histone deacetylase 1), VHL (von Hippel-Lindau tumor suppressor), MAD2L2 (Mitotic Arrest Deficient 2 Like 2), CEBPA (CCAAT/enhancer-binding protein alpha), CHMP4A, CHMP5, CHMP2A, CHMP3 and ENSG00000249884 (RNF103-CHMP3 gene), all of them are well-known in carcinogenesis. Although this study was based on in silico evaluations, our findings can open a new window for researchers of HCC to focus on such candidate genes during experimental assays.