Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients.

Kahles A, Lehmann KV, Toussaint NC, Hüser M, Stark SG, Sachsenberg T, Stegle O, Kohlbacher O, Sander C, Cancer Genome Atlas Research Network, Rätsch G
Cancer Cell. 2018 34 (2): 211-224.e6

PMID: 30078747 · DOI:10.1016/j.ccell.2018.07.001

Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects alternative splicing events and tumor variants by reanalyzing RNA and whole-exome sequencing data. Tumors have up to 30% more alternative splicing events than normal samples. Association analysis of somatic variants with alternative splicing events confirmed known trans associations with variants in SF3B1 and U2AF1 and identified additional trans-acting variants (e.g., TADA1, PPP2R1A). Many tumors have thousands of alternative splicing events not detectable in normal samples; on average, we identified ≈930 exon-exon junctions ("neojunctions") in tumors not typically found in GTEx normals. From Clinical Proteomic Tumor Analysis Consortium data available for breast and ovarian tumor samples, we confirmed ≈1.7 neojunction- and ≈0.6 single nucleotide variant-derived peptides per tumor sample that are also predicted major histocompatibility complex-I binders ("putative neoantigens").

Copyright © 2018 Elsevier Inc. All rights reserved.

MeSH Terms (7)

Alternative Splicing Humans Neoplasms Polymorphism, Single Nucleotide Quantitative Trait Loci Sequence Analysis, RNA Whole Exome Sequencing

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