Defective transcription elongation in a subset of cancers confers immunotherapy resistance.

ABSTRACT: The nature and role of global transcriptional deregulations in cancers are not fully understood. We report that a large proportion of cancers have widespread defects in mRNA transcription elongation (TE). Cancers with TE defects (TE^deff) display spurious transcription and defective mRNA processing of genes characterized by long genomic length, poised promoters and inducible expression. Signaling pathways regulated by such genes, such as pro-inflammatory response pathways, are consistently suppressed in TE^deff tumors. Remarkably, TE^deff correlates with the poor response and outcome in immunotherapy, but not chemo- or targeted therapy, -treated renal cell carcinoma and metastatic melanoma patients. Forced pharmacologic or genetic induction of TE^deff

SUBMITTER: Modur V 

PROVIDER: S-EPMC6199328 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature