Abstract:
:Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer.
journal_name
Elifejournal_title
eLifeauthors
Grosso AR,Leite AP,Carvalho S,Matos MR,Martins FB,Vítor AC,Desterro JM,Carmo-Fonseca M,de Almeida SFdoi
10.7554/eLife.09214subject
Has Abstractpub_date
2015-11-17 00:00:00issn
2050-084Xjournal_volume
4pub_type
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