Profiling of exome mutations associated with progression of HBV-related hepatocellular carcinoma.

Abstract

Recent advances in sequencing technology have allowed us to profile genome-wide

mutations of various cancer types, revealing huge heterogeneity of cancer genome

variations. However, its heterogeneous landscape of somatic mutations according

to liver cancer progression is not fully understood. Here, we profiled the

mutations and gene expressions of early and advanced hepatocellular carcinoma

(HCC) related with Hepatitis B-viral infection. Integrative analysis was

performed with whole-exome sequencing and gene expression profiles of the 12

cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues. A

total of 293 tumor-specific somatic variants and 202 non-tumoral variants were

identified. The tumor-specific variants were found to be enriched at chromosome

1q particularly in the advanced HCC, compared to the non-tumoral variants.

Functional enrichment analysis revealed frequent mutations at the genes encoding

cytoskeleton organization, cell adhesion, and cell cycle-related genes. In

addition, to elucidate actionable somatic mutations, we performed an integrative

analysis of gene mutations and gene expression profiles together. This revealed

the 48 mutated genes which were differentially mutated with concomitant gene

expression enrichment. Of these, CTNNB1 was found to have a pivotal role in the

differential progression of the HCC subgroup. In conclusion, our integrative

analysis of whole-exome sequencing and transcriptome profiles could provide

actionable mutations which might play pivotal roles in the heterogeneous

progression of HCC.