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”). A pan-cancer analysis by Kahles et al. shows increased alternative splicing events in tumors versus normal tissue and identifies trans-acting variants associated with alternative splicing events. Tumors contain neojunction-derived peptides absent in normal samples, including predicted MHC-I binders that are putative neoantigens.

Original languageEnglish
Pages (from-to)211-224.e6
JournalCancer Cell
Issue number2
StatePublished - Aug 13 2018


  • GTEx
  • MS proteomics
  • RNA-seq
  • TCGA
  • TCGA Pan-Cancer Atlas
  • alternative splicing
  • cancer
  • exome
  • immunoediting
  • immunotherapy
  • neoantigens
  • splicing QTL
  • tumor-specific splicing


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