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

Journal Article (Journal Article)

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").

Full Text

Duke Authors

Cited Authors

  • Kahles, A; Lehmann, K-V; Toussaint, NC; Hüser, M; Stark, SG; Sachsenberg, T; Stegle, O; Kohlbacher, O; Sander, C; Cancer Genome Atlas Research Network, ; Rätsch, G

Published Date

  • August 13, 2018

Published In

Volume / Issue

  • 34 / 2

Start / End Page

  • 211 - 224.e6

PubMed ID

  • 30078747

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2018.07.001


  • eng

Conference Location

  • United States