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| Status |
Public on Nov 17, 2015 |
| Title |
Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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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| |
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| Overall design |
RNA-seq of SETD2 mutant and wild-type ccRCC cell lines.
|
| |
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| Contributor(s) |
Grosso AR, Leite AP, Carvalho S, Matos M, Martins FB, Vitor AC, Desterro J, Carmo-Fonseca M, de Almeida SF |
| Citation(s) |
26575290 |
| |
| Submission date |
Dec 22, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Ana Rita Grosso |
| E-mail(s) |
argrosso@fct.unl.pt
|
| Organization name |
Unidade de Ciências Biomoleculares Aplicadas (UCIBIO)/Faculdade de Ciências e Tecnologia - Universidade Nova de Lisboa
|
| Department |
Departamento Ciências da Vida
|
| Lab |
Computational Multi-omics Lab
|
| Street address |
Campus de Caparica
|
| City |
Almada |
| ZIP/Postal code |
2829-516 |
| Country |
Portugal |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA271032 |
| SRA |
SRP051485 |
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