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Cell Rep. 2017 Aug 29;20(9):2215-2226. doi: 10.1016/j.celrep.2017.08.012.

The Functional Impact of Alternative Splicing in Cancer.

Author information

1
Computational RNA Biology Group, Pompeu Fabra University (UPF), 08003 Barcelona, Spain; MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology, 77300 Fontainebleau, France; Institut Curie, 75248 Paris Cedex, France; INSERM U900, 75248 Paris Cedex, France.
2
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Barcelona Supercomputing Centre (BSC), 08034 Barcelona, Spain.
3
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
4
Computational RNA Biology Group, Pompeu Fabra University (UPF), 08003 Barcelona, Spain; Catalan Institution of Research and Advanced Studies (ICREA), 08010 Barcelona, Spain. Electronic address: eduardo.eyras@upf.edu.

Abstract

Alternative splicing changes are frequently observed in cancer and are starting to be recognized as important signatures for tumor progression and therapy. However, their functional impact and relevance to tumorigenesis remain mostly unknown. We carried out a systematic analysis to characterize the potential functional consequences of alternative splicing changes in thousands of tumor samples. This analysis revealed that a subset of alternative splicing changes affect protein domain families that are frequently mutated in tumors and potentially disrupt protein-protein interactions in cancer-related pathways. Moreover, there was a negative correlation between the number of these alternative splicing changes in a sample and the number of somatic mutations in drivers. We propose that a subset of the alternative splicing changes observed in tumors may represent independent oncogenic processes that could be relevant to explain the functional transformations in cancer, and some of them could potentially be considered alternative splicing drivers (AS drivers).

KEYWORDS:

TCGA; alternative splicing; cancer; cancer drivers; isoform switch; networks; protein domains; protein-protein interactions; transcript isoforms

PMID:
28854369
DOI:
10.1016/j.celrep.2017.08.012
[Indexed for MEDLINE]
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