Extended Data Fig. 6: FOXA1 mutations in CPGEA.
From: A genomic and epigenomic atlas of prostate cancer in Asian populations
a, FOXA1 mutation validation. Two representative validations by Sanger sequencing and reconstructed RNA-seq analysis. b, Validation of a FOXA1 in-frame deletion-derived peptide by mass spectrometry. c, Mapping of FOXA1 mutations onto the three-dimensional structure of FOXA1 and bound DNA (based on PDB registry 1VTN78). d, DNA methylation over FOXA1-binding sites in tumours with FOXA1 truncation/in-frame deletion. Top, FOXA1-binding motifs in the ENCODE chromatin immunoprecipitation with high-throughput sequencing (ChIP–seq) dataset (left) versus FOXA1-binding motifs outside of FOXA1 ChIP–seq peaks (right). Bottom, wild-type FOXA1-binding sites (left) and mutant FOXA1-binding sites (right) from recently published ChIP–seq data38. P values were determined by one-sided Mann–Whitney U-tests. Box plots are as in Fig. 4b. Each dot corresponds to a normal or tumour sample. e, Clonal analysis of FOXA1 in CPGEA. f, Mutual exclusivity or co-occurrence of gene alterations between genes belonging to 12 important curated pathways. Only alterations with at least one significant interaction (P < 0.05) are included. Asterisks indicate significant relationships. g, Allele frequency distribution of FOXA1 mutations in CPGEA and TCGA processed with the CPGEA pipeline. h, Significant mutual exclusions and co-occurrences between FOXA1 mutations and other genetic lesions in CPGEA, identified by OncoPrint from cBioPortal92. i, FOXA1 mutations and downstream pathways. Pairwise comparison of expression levels of important pathways. The z-score of specific genes and clinical features are displayed in a heat map grouped by different mutation subtypes.
