Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma
- Faculdade de Medicina da Universidade de Lisboa, Portugal
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.
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© 2015, Grosso et al.
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Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma
eLife 4:e09214.
https://doi.org/10.7554/eLife.09214
