Pluto Bioinformatics

GSE145316: Pan-cancer molecular analysis of the RB-pathway

Bulk RNA sequencing

The retinoblastoma tumor suppressor (RB1) plays a critical role in coordinating multiple pathways that impact on tumor initiation, disease progression, and therapeutic responses. Here we interrogated the TCGA pan-cancer data collection to probe fundamental molecular features associated with the RB-pathway across 31 tumor-types.; While the RB-pathway has been purported to exhibit multiple mutually exclusive events, only RB1 is mutually exclusive with multiple genetic events that deregulate CDK4/6 activity. Using an isogenic ER+ breast cancer model with targeted RB1 deletion, we identified gene expression features that link CDK4/6 activity and RB-dependency (CDK4/6-RB integrated signature). This gene expression signature is associated with prognosis across a spectrum of tumors that exhibit average lower signature value indicative of more indolent diseases.; Single copy loss on chromosome 13q encompassing the RB1 locus is prevalent in many cancers, and is associated with reduced expression of multiple genes on 13q including RB1, and inversely related to the CDK4/6-RB integrated signature supporting a genetic cause/effect relationship.; To probe the broader implications on tumor biology, we investigated genes that are positively and inversely correlated with the CDK4/6-RB integrated signature. This approach defined tumor-specific pathways that could represent new therapeutic vulnerabilities associated with RB-pathway activity. SOURCE: Ram,Mohan,Nambiar ( - Roswell Park

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