Recurrent alternative splicing isoform switches in tumor samples provide novel signatures of cancer

BioRxiv : the Preprint Server for Biology
E SebestyénE Eyras

Abstract

Cancer genomics has been instrumental to determine the genetic alterations that are predictive of various tumor conditions. However, the majority of these alterations occur at low frequencies, motivating the need to expand the catalogue of cancer signatures. Alternative pre-mRNA splicing alterations, which bear major importance for the understanding of cancer, have not been exhaustively studied yet in the context of recent cancer genome projects. In this article we analyze RNA sequencing data for more than 4000 samples from The Cancer Genome Atlas (TCGA) project, including paired normal samples, to detect recurrent alternative splicing isoform switches in 9 different cancer types. We first investigate whether alternative splicing isoform changes are predictive of tumors by applying a rank-based algorithm based on the reversal of the relative expression of transcript isoforms. We find that consistent alternative splicing isoform changes can separate with high accuracy tumor and normal samples, as well as some cancer subtypes. We then searched for those changes that occur in the most abundant isoform, i.e isoform switches, and are therefore more likely to have a functional impact. In total we detected 244 isoform switches, which ...Continue Reading

Related Concepts

Malignant Neoplasms
Exons
Genome
Neoplasms
RNA Splicing
Computer Software
Tumor Suppressor Genes
Subtype (Attribute)
Tumor Tissue Sample
Somatic Mutation

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