Extended Data Fig. 2: Genomic characteristics of the three classes of FOXA1 alterations in prostate and breast cancer.
From: Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer
a, b, Bi-allelic inactivation (a) and copy-number variations (b) of FOXA1 across mCRPC (n = 371). CN-LOH, copy-neutral loss of heterozygosity. c, FOXA1 expression (RNA-seq) in benign (n = 51), primary (n = 501) and metastatic (n = 535) prostate cancer. d, Distribution and functional categorization of FOXA1 mutations (all cases in the aggregate cohort) on the protein map of FOXA1. e, Aggregate and class-specific distribution of FOXA1 mutations in advanced breast cancer (MSK-IMPACT cohort). f, Structural classification of FOXA1 locus rearrangements in breast cancer (TCGA and CCLE cell lines). g, h, Variant allele frequency of FOXA1 mutations by tumour stage (g) and clonality estimates of class-1 and class-2 mutations (h) in tumour-content-corrected primary prostate cancer (n = 500) and mCRPC (n = 370) specimens. i, Mutual exclusivity or co-occurrence of FOXA1 mutations (two-sided Fisher’s exact test). Mutations in AR, WNT, and PI3K were aggregated at the pathway level. ETS, ETS gene fusions; DRD, DNA repair defects and included alterations in BRCA1, BRCA2, ATM and CDK12; MMRD, mismatch repair deficiency (total n = 371). j, Mutual exclusivity of ETS and/or SPOP (n = 26) alterations with FOXA1 (n = 46) alterations distinguished by class in mCRPC (n = 371). k, Co-occurrence of WNT (n = 58) and DRD (n = 107) pathway alterations with FOXA1 alteration classes in mCRPC (n = 371). l, Stage- and class-specific increase in FOXA1 expression levels in primary (n = 500) and metastatic prostate cancer (n = 357). Left, two-sided t-test. Right, two-way ANOVA. For all box plots, centre shows median, box marks quartiles 1–3 and whiskers span quartiles 1–3 ± 1.5 × IQR.
