Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma.
Elife
; 42015 Nov 17.
Article
em En
| MEDLINE
| ID: mdl-26575290
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recombinação Genética
/
Transcrição Gênica
/
RNA Mensageiro
/
Carcinoma de Células Renais
/
Expressão Gênica
/
Proteínas Oncogênicas
/
Neoplasias Renais
Limite:
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Portugal