SPEN

Overview

SPEN (SHARP/MINT) is a hormone-inducible transcription repressor. In the corpus it is recurrently mutated in anaplastic thyroid carcinoma and in prostate cancer patient-derived xenografts, implicating its role in hormone signaling regulation across cancer types.

Alterations observed in the corpus

  • SPEN was identified among recurrent SNVs by SeqSig analysis in anaplastic thyroid carcinoma (ATC) across the genomic and evolutionary landscape study of ATC PMID:38412093.
  • SPEN mutations were detected in prostate cancer PDX heterogeneity pairs (cases 146 and 316); SPEN is implicated as a hormone-inducible transcription repressor in prostate cancer PMID:38488813.
  • 8 total truncating mutations in adenoid cystic carcinoma (6 in discovery, 2 in extension cohort); all premature stops upstream of the SPOC domain; no consistent LOH; co-occurring with NOTCH2 truncations in one case (PD3189); enriched in solid-histology ACC (worse prognosis); implicates NOTCH-pathway abrogation. PMID:23778141
  • Mutated in 2/21 sequenced sinonasal adenoid cystic carcinomas (AdCC; 9%); frameshift duplications c.2918dup (p.Ser974LysfsTer48) and c.2906del (p.Pro969LeufsTer5) PMID:24418857
  • Somatic mutations in SPEN enriched in adenoid cystic carcinomas (ACC) lacking both MYB and MYBL1 fusions, suggesting NOTCH-pathway preferential involvement in the fusion-negative ACC subset PMID:26631609
  • SPEN loss-of-function mutations contribute to constitutive Notch activation in grade-3 adenoid cystic carcinoma (ACC); SPEN or NOTCH1 alterations found in 7/9 grade-3 tumors PMID:26829750
  • Newly implicated tumor suppressor in DLBCL with truncating mutations and CN loss PMID:28985567
  • SPEN mutated in 2.4% of prostate cancer cohort, predominantly truncating and clonal; significantly enriched in metastatic samples (q=0.008). Encodes a hormone-inducible transcriptional repressor; nominated as a driver in advanced/metastatic prostate cancer PMID:29610475

Cancer types (linked)

  • THPA — recurrent SNV in ATC identified by SeqSig analysis PMID:38412093.
  • PRAD — mutations in PDX heterogeneity pairs; role as hormone-responsive transcription repressor PMID:38488813.

Co-occurrence and mutual exclusivity

  • In ATC, SPEN mutations co-occur with TP53, BRAF V600E, and other ATC drivers in the genomic landscape PMID:38412093.

Therapeutic relevance

  • No direct targeted therapy reported in the corpus; SPEN’s role as a hormone-inducible repressor may be relevant to AR-directed therapies in prostate cancer PMID:38488813.

Open questions

  • Frequency and prognostic significance of SPEN mutations in ATC and prostate cancer require validation in larger cohorts PMID:38412093 PMID:38488813.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:24418857

This page was processed by crosslinker on 2026-05-14. - PMID:26631609

This page was processed by crosslinker on 2026-05-14. - PMID:26829750

This page was processed by wiki-cli on 2026-05-14. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15. - PMID:29610475

This page was processed by wiki-cli on 2026-05-15.