Exon-Level Microarray Analyses Identify Alternative Splicing Programs in Breast Cancer

摘要: Protein isoforms produced by alternative splicing (AS) of many genes have been implicated in several aspects cancer genesis and progression. These observations motivated a genome-wide assessment AS breast cancer. We accomplished this measuring exon level expression 31 nonmalignant immortalized cell lines representing luminal, basal, claudin-low subtypes using Affymetrix Human Junction Arrays. analyzed these data computational pipeline specifically designed to detect with low false-positive rate. This identified 181 splice events 156 as candidates for AS. Reverse transcription-PCR validation subset predicted confirmed 90%. Approximately half the were associated or subtypes. Exons involved subtype–specific significantly presence evolutionarily conserved binding motifs tissue-specific Fox2 factor. Small interfering RNA knockdown involvement factor subtype-specific The detected study likely reflects pattern progenitor cells which tumor arose suggests utility assays Fox-mediated subtype definition early detection. also suggest possibility reducing toxicity protein-targeted treatments targeting protein that are not present limiting normal tissues.