Genomic alterations across six hepatocellular carcinoma cell lines by panel-based sequencing

Author:Zhao Y, Chen Y,Hu Y,et al.

Background: Current sequencing efforts have revealed the mutational landscape of patients with hepatocellular carcinoma (HCC). However, genetic alterations in human HCC cellular models have remained unclear. 

Methods: We present a panel-based sequencing method to identify somatic mutations in six human hepatoma cell lines (HuH-7, Hep3B, SK-HEP-1, MHCC97, HepG2 and HepG2.2.15). Target enrichments from a genomic library of captured exons of 325 mutated genes in various types of cancer were then used for paired-end sequencing. 

Results: This method exhibited a 99.7% average coverage rate in target regions with an approximately 1,000 read depth. We discovered 344 somatic non-synonymous variations in 100 genes. Among these genes, 38 significantly altered cancer-related genes were identified and enriched in the following five oncogenic pathways: chromatin remodeling, Notch, MAPK, p53 cell cycle and Wnt/β-catenin. Four cell lines (HuH-7, Hep3B, SK-HEP-1 and HepG2) established from different HCC individuals had different mutational patterns. 

However, genomic alterations in two series of cell lines from parent MHCC97 and HepG2 cells both showed similarities and some minor discrepancies. 

Conclusions: Our panel-based sequencing analysis of HCC cell lines identified genomic alterations in HCC experimental cellular models as well as the mutational patterns of cells from different and same clone origins. These investigations of HCC cell lines provide new insights into the understanding the genetic heterogeneity and clonal evolution of liver cancer.