The pattern of gene copy number alteration (CNAs) in hepatocellular carcinoma: an in silico analysis

Molecular Cytogenetics - Tập 14 - Trang 1-10 - 2021
Arman Shahrisa1, Maryam Tahmasebi-Birgani2,3, Hossein Ansari4, Zahra Mohammadi5, Vinicio Carloni6, Javad Mohammadi Asl1
1Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4Department of Biotechnology, Islamic Azad University, Ahvaz Branch, Ahvaz, Iran
5School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
6Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

Tóm tắt

Hepatocellular carcinoma (HCC) is the most common type of liver cancer that occurs predominantly in patients with previous liver conditions. In the absence of an ideal screening modality, HCC is usually diagnosed at an advanced stage. Recent studies show that loss or gain of genomic materials can activate the oncogenes or inactivate the tumor suppressor genes to predispose cells toward carcinogenesis. Here, we evaluated both the copy number alteration (CNA) and RNA sequencing data of 361 HCC samples in order to locate the frequently altered chromosomal regions and identify the affected genes. Our data show that the chr1q and chr8p are two hotspot regions for genomic amplifications and deletions respectively. Among the amplified genes, YY1AP1 (chr1q22) possessed the largest correlation between CNA and gene expression. Moreover, it showed a positive correlation between CNA and tumor grade. Regarding deleted genes, CHMP7 (chr8p21.3) possessed the largest correlation between CNA and gene expression. Protein products of both genes interact with other cellular proteins to carry out various functional roles. These include ASH1L, ZNF496, YY1, ZMYM4, CHMP4A, CHMP5, CHMP2A and CHMP3, some of which are well-known cancer-related genes. Our in-silico analysis demonstrates the importance of copy number alterations in the pathology of HCC. These findings open a door for future studies that evaluate our results by performing additional experiments.

Tài liệu tham khảo