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

André Kahles; Kjong-Van Lehmann; Nora C Toussaint; Matthias Hüser; Stefan G Stark; Timo Sachsenberg; Oliver Stegle; Oliver Kohlbacher; Chris Sander; Gunnar Rätsch

doi:10.1016/j.ccell.2018.07.001

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

Journal article

Open access

Peer reviewed

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

André Kahles, Kjong-Van Lehmann, Nora C Toussaint, Matthias Hüser, Stefan G Stark, Timo Sachsenberg, Oliver Stegle, Oliver Kohlbacher, Chris Sander and Gunnar Rätsch

Cancer cell, Vol.34(2), pp.211-224.e6

08/13/2018

DOI: 10.1016/j.ccell.2018.07.001

PMID: 30078747

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Abstract

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").

Alternative Splicing

Humans

Neoplasms - genetics

Polymorphism, Single Nucleotide

Quantitative Trait Loci

Sequence Analysis, RNA

Whole Exome Sequencing

Details

Title: Subtitle: Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients
Creators: André Kahles - Memorial Sloan Kettering Cancer Center
Kjong-Van Lehmann - Memorial Sloan Kettering Cancer Center
Nora C Toussaint - SIB Swiss Institute of Bioinformatics
Matthias Hüser - SIB Swiss Institute of Bioinformatics
Stefan G Stark - Memorial Sloan Kettering Cancer Center
Timo Sachsenberg - University of Tübingen
Oliver Stegle - European Bioinformatics Institute
Oliver Kohlbacher - University of Tübingen
Chris Sander - Harvard University
Gunnar Rätsch - Memorial Sloan Kettering Cancer Center
Contributors: Cancer Genome Atlas Research Network
Deqin Ma - University of Iowa, Pathology
Mohammed M Milhem - University of Iowa, Internal Medicine
Aaron D Bossler - University of Iowa, Pathology
Resource Type: Journal article
Publication Details: Cancer cell, Vol.34(2), pp.211-224.e6
DOI: 10.1016/j.ccell.2018.07.001
PMID: 30078747
NLM abbreviation: Cancer Cell
ISSN: 1535-6108
eISSN: 1878-3686
Grant note: K08 NS045077 / NINDS NIH HHS R01 NS081125 / NINDS NIH HHS
Language: English
Date published: 08/13/2018
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
Record Identifier: 9984185178702771

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