Biochemistry, Biophysics, and Structural Biology Commons^™

Splicing Mutation Analysis Reveals Previously Unrecognized Pathways In Lymph Node-Invasive Breast Cancer., Stephanie N Dorman, Coby Viner, Peter K Rogan

Biochemistry Publications

Somatic mutations reported in large-scale breast cancer (BC) sequencing studies primarily consist of protein coding mutations. mRNA splicing mutation analyses have been limited in scope, despite their prevalence in Mendelian genetic disorders. We predicted splicing mutations in 442 BC tumour and matched normal exomes from The Cancer Genome Atlas Consortium (TCGA). These splicing defects were validated by abnormal expression changes in these tumours. Of the 5,206 putative mutations identified, exon skipping, leaky or cryptic splicing was confirmed for 988 variants. Pathway enrichment analysis of the mutated genes revealed mutations in 9 NCAM1-related pathways, which were significantly increased in samples with …