HOXB13

Overview

HOXB13 (Homeobox B13) encodes a homeobox transcription factor expressed in the prostate and known to interact with androgen receptor signaling. Germline variants in HOXB13 — most notably G84E — are established hereditary prostate cancer susceptibility alleles. HOXB13 is enriched among presumed pathogenic germline mutations (PPGMs) in metastatic prostate cancer cohorts.

Alterations observed in the corpus

  • Germline presumed pathogenic variant (PPGM) in 3/500 patients (5% of PPGM carriers) in the MET500 metastatic solid tumor cohort; identified as a non-DNA-repair prostate-cancer susceptibility allele, significantly enriched relative to ExAC controls PMID:28783718.

Cancer types (linked)

  • PRAD: Germline HOXB13 pathogenic variants enriched in metastatic prostate cancer (n=3 PPGM carriers in MET500, 5% of all PPGMs); established prostate-cancer susceptibility allele PMID:28783718.

Co-occurrence and mutual exclusivity

  • No co-occurrence or mutual exclusivity data reported in the corpus to date beyond its categorization as a non-DNA-repair PPGM.

Therapeutic relevance

  • Germline HOXB13 carrier status has implications for genetic counseling and cascade testing; no direct targeted therapy reported in the corpus.

Open questions

  • Whether germline HOXB13 variants affect response to androgen-receptor-directed therapies or PARP inhibitors in metastatic prostate cancer remains to be established.

Sources

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