Abstract Purpose: Around 10% to 15% of prostate cancers harbor recurrent aberrations in the Forkhead Box A1 gene, FOXA1, whereby the alteration type and the effect on the forkhead (FKH) domain affect protein function. We developed a FOXA1 classification system to inform clinical management. Experimental Design: A total of 5,014 prostate cancer samples were examined using whole-exome and -transcriptome sequencing from the Caris Life Sciences database. We denoted class 1 FOXA1 alterations as missense and in-frame in…

<p>Molecular associations by <i>FOXA1</i> alteration class. Percentages of (<b>A</b>) <i>TMPRSS2–ERG</i> fusions, (<b>B</b>) <i>TP53</i> mutations, (<b>C</b>) MSI-high status, and (<b>D</b>) TMB-high status based on <i>FOXA1</i> alteration classes. All <i>q</i> values are relative to WT cases. Percentages of select genetic alterations comparing WT and (<b>E</b>) class 1B, (<b>F</b&…

<p><i>FOXA1</i> alterations in prostate cancer. <b>A,</b> Bar graphs showing percentages of amplifications and mutations found in the top 20 cancers with <i>FOXA1</i> alterations from the Caris Life Sciences POA database. CUP, carcinoma of unknown primary; CRC, colorectal cancer; FGTM, female genital tract malignancy; H&N, head and neck; MCC, Merkel cell carcinoma; MGTM, male genital tract malignancy; NE, neuroendocrine; NSCLC, non–small cell lung cancer; SCLC, small c…

<p><i>FOXA1</i> alteration classes by race. <b>A, </b><i>FOXA1</i> alteration classes are examined by race. <b>B,</b> The distribution of <i>FOXA1</i> alteration classes by race. *q value <0.05, **q value <0.01, ***q value < 0.001, ****q value < 0.0001. </p>

<p>Supplementary Tables 1-11</p>