Splicing, Mutation, and Methylation Alterations Drive Gene Expression in HPV-OPC more than Copy Number Variation: A Network Propagation Analysis

Compared with traditional tobacco- and alcohol-associated head and neck cancer, Human papillomavirus-related oropharynx cancer (HPVOPC) tumors have relatively few alteration events. Attention is often directed toward single nucleotide variation (SNV) or gene mutation as a primary driver of carcinogenesis, although there are other potential drivers of oncogenic gene expression, including DNA methylation, alternative splicing events (ASE), and copy number variation (CNV). The relative contribution of these classes of cancer alterations in driving genome wide differential gene expression (DEG) in HPVOPC is unclear. We employed genome wide network analyses to integrate tumor alteration events with gene interaction networks to investigate what classes of alterations drive global DEG output in HPVOPC. We hypothesize that genome wide ASE, methylation, and CNV alterations, in addition to SNV alterations, may be closely correlated with DEG, implicating these alterations as primary drivers of altered gene expression.