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Comprehensive analysis of alternative splicing across tumors from 8,705 patients

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Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients.pdfPublished version44.47 MBAdobe PDFView/Open
Title: Comprehensive analysis of alternative splicing across tumors from 8,705 patients
Authors: Kahles, A
Lehmann, K-V
Toussaint, NC
Huser, M
Stark, SG
Sachsenberg, T
Stegle, O
Kohlbacher, O
Sander, C
Ratsch, G
Item Type: Journal Article
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”).
Issue Date: 13-Aug-2018
Date of Acceptance: 2-Jul-2018
URI: http://hdl.handle.net/10044/1/71274
DOI: https://doi.org/10.1016/j.ccell.2018.07.001
ISSN: 1535-6108
Publisher: Elsevier (Cell Press)
Start Page: 211
End Page: 224
Journal / Book Title: Cancer Cell
Volume: 34
Issue: 2
Copyright Statement: © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
BREAST-CANCER
COWDEN-SYNDROME
SOMATIC MUTATIONS
MASS-SPECTROMETRY
MET INHIBITORS
OVARIAN-CANCER
IDENTIFICATION
PTEN
VARIANTS
REVEALS
CPTAC
GTEx
MS proteomics
RNA-seq
TCGA
TCGA Pan-Cancer Atlas
alternative splicing
cancer
exome
immunoediting
immunotherapy
neoantigens
splicing QTL
tumor-specific splicing
Alternative Splicing
Humans
Neoplasms
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Sequence Analysis, RNA
Whole Exome Sequencing
Cancer Genome Atlas Research Network
Humans
Neoplasms
Sequence Analysis, RNA
Alternative Splicing
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Whole Exome Sequencing
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
BREAST-CANCER
COWDEN-SYNDROME
SOMATIC MUTATIONS
MASS-SPECTROMETRY
MET INHIBITORS
OVARIAN-CANCER
IDENTIFICATION
PTEN
VARIANTS
REVEALS
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
1109 Neurosciences
Publication Status: Published
Open Access location: https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30306-4
Online Publication Date: 2018-08-02
Appears in Collections:Department of Surgery and Cancer