The Functional Impact of Alternative Splicing in Cancer

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Héctor Climente-González, Eduard Porta-Pardo, Adam Godzik, Eduardo Eyras
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).

Graphical abstract

Teaser

Climente-González et al. show that alternative splicing (AS) changes in tumors are linked to a significant loss of functional domain families that are also frequently mutated in cancer. These domain losses happen independently of somatic mutations and lead to the remodeling of complexes and protein-protein interactions in cancer.


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