Cancer-Specific Splicing Changes and the Potential for Splicing-Derived Neoantigens

Abstract

In this issue of Cancer Cell, Kahles et al. perform a comprehensive analysis of RNA splicing across cancer types and identify novel correlations between genetic alterations and splicing in cancer. In addition, they identify that tumor-specific splicing has the potential to generate a large new class of tumor-specific neoantigens.

Figure 1.. Integrating WES and RNA-Seq with Proteomics Data from The Cancer Genome Atlas to Identify the Full Complement of Aberrant Splicing Changes in Cancer and the Extent to which These Changes Generate Splicing-Derived Neoantigens

Kahles et al. utilized WES and RNA-seq data from 8,705 patients and 670 matched normal controls from TCGA, along with complementary RNA-seq of normal tissues from the GTEx project and proteomic data from TCGA breast and ovarian tumors from CPTAC. These data were integrated to determine qualitative differences in splicing between tumor and normal tissue in different cancer types (top left). In addition, the authors performed a splicing quantitative trait loci (sQTL) study to associate genomic variants with splicing changes in tumor versus normal (top right). Data from the first aim were then used to identify cancer-specific exon-exon junctions (bottom left). Finally, through in silico analyses, the authors evaluated the extent to which these exon-exon junctions are translated to cancer-specific antigens that could be presented on MHC-I (bottom right).