Frequent FOXA1-Activating Mutations in Extramammary Paget's Disease.

ABSTRACT: Extramammary Paget's disease (EMPD) is a neoplastic skin disease of indeterminate origin with an unknown genetic cause. We performed a comprehensive genetic analysis or targeted gene sequencing in 48 patients with EMPD. We identified FOXA1 mutations, a GAS6-FOXA1 fusion gene, and somatic hotspot mutations in the FOXA1 promoter region in 11 of the 48 EMPD patients (11/48, 23%). Additional mutations were identified in PIK3CA (six patients) and in HIST1H2BB, HIST1H2BC, and SMARCB1 (one patient each), but none were found in other frequently mutated genes in cancer. A global gene expression analysis using EMPD clinical samples found the upregulation of PI3 kinase-AKT-mTOR signaling. ABCC11, which is specifically expressed in the apocrine s

SUBMITTER: Takeichi T 

PROVIDER: S-EPMC7226542 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature