Structurally Oriented Classification of FOXA1 Alterations Identifies Prostate Cancers with Opposing Clinical Outcomes and Distinct Molecular and Immunologic Subtypes.

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 insertions/deletions with subclasses oriented with respect to the FKH domain. These were in the first part of the FKH domain [class 1A: amino acids (AA) 168-246], within the Wing2 region of FKH (class 1B: AA 247-269), or outside FKH (class 1C: AA 1-167, 270+). Two hotspot missen

SUBMITTER: Hwang J 

PROVIDER: S-EPMC11873805 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature