In-depth genomic data analyses revealed complex transcriptional and epigenetic dysregulations of BRAFV600E in XXXX .

@entity3060 @entity5 @entity7097 @entity8554 @entity2533 @entity817 @entity15786 @entity320
BACKGROUND: The recurrent @entity817 driver mutation @entity8554 ( @entity817 ( @entity8554 )) is currently one of the most clinically relevant mutations in @entity320 . However, the genome-wide transcriptional and epigenetic dysregulations induced by @entity817 ( @entity8554 ) are still unclear. The investigation of this driver mutation's functional consequences is critical to the understanding of tumorigenesis and the development of therapeutic strategies. METHODS AND RESULTS: We performed an integrative analysis of transcriptomic and epigenomic changes disturbed by @entity817 ( @entity8554 ) by comparing the gene expression and methylation profiles of 34 primary @entity320 harboring @entity817 ( @entity8554 ) with those of 27 @entity817 ( @entity7097 ) samples available from The @entity5 (TCGA). A total of 711 significantly differentially expressed genes were identified as putative @entity817 ( @entity8554 ) target genes. Functional enrichment analyses revealed the transcription factor @entity3060 (p   <   3.6 * 10(-16)) and growth factor @entity2533 (p   <   3.1 * 10(-9)) were the most significantly enriched up-regulators, with @entity3060 being significantly up-regulated, whereas @entity2533 was significantly down-regulated in @entity817 ( @entity8554 ), suggesting that they may mediate tumorigenesis driven by @entity817 ( @entity8554 ). Further investigation using the @entity3060 ChIP-Seq data confirmed that @entity817 ( @entity8554 ) led to an overall increased level of gene expression for the @entity3060 targets. Furthermore, DNA methylation analysis revealed a global DNA methylation loss in @entity817 ( @entity8554 ) relative to @entity817 ( @entity7097 ). This might be due to @entity817 dysregulation of @entity15786 , which was identified as a potential target with significant down-regulation in @entity817 ( @entity8554 ). Finally, we demonstrated that @entity817 ( @entity8554 ) targets may play essential functional roles in cell growth and proliferation, measured by their effects on @entity320 growth using a short hairpin RNA silencing experimental dataset. CONCLUSIONS: Our integrative analysis identified a set of @entity817 ( @entity8554 ) target genes. Further analyses suggested a complex mechanism driven by mutation @entity817 ( @entity8554 ) on @entity320 that disturbs specific @entity5 -related genes, pathways, and methylation modifications.
