A pan-cancer analysis of driver gene mutations, DNA methylation and gene expressions reveals that chromatin remodeling is a major mechanism inducing global changes in cancer epigenomes

摘要: Recent large-scale cancer sequencing studies have discovered many novel driver genes (CDGs) in human cancers. Some also suggest that CDG mutations contribute to cancer-associated epigenomic and transcriptomic alterations across types. Here we aim improve our understanding of the connections between altered cell epigenomes transcriptomes on pan-cancer level how these known association epigenome transcriptome. Using multi-omics data including somatic mutation, DNA methylation, gene expression 20 types from The Cancer Genome Atlas (TCGA) project, conducted a analysis identify CDGs, when mutated, strong associations with genome-wide methylation or changes types, which refer as (MDGs) (EDGs), respectively. We identified 32 MDGs, among which, eight are chromatin modification remodeling genes. Many remaining 24 MDGs connected regulators through either regulating their transcription physically interacting them potential co-factors. 29 EDGs, 26 MDGs. Further investigation target genes’ promoters alteration patterns overlapping shows hyper-methylation significantly associated down-regulation same hypo-methylation up-regulation This finding suggests pivotal role for genetically driven shaping during tumor development.