SPOP

Overview

SPOP is a substrate-binding adaptor for a Cullin3-based E3 ubiquitin ligase complex and is one of the most frequently mutated genes in prostate adenocarcinoma. In the corpus it was detected in prostate cancer patient-derived xenograft (PDX) models.

Alterations observed in the corpus

  • SPOP mutations were detected in the prostate cancer PDX heterogeneity pair 316 (MDA PCa PDX series, n=37 models); SPOP is a known prostate cancer tumor suppressor PMID:38488813.
  • Recurrent missense mutations in the MATH domain substrate-binding cleft (Y87, W131, F133 and others; F133V most common); mutant SPOP increases cell invasion in vitro; mutated in 6-15% of prostate cancers across cohorts; defines a molecular subtype mutually exclusive with ETS rearrangements PMID:22610119
  • SPOP carries recurrent point mutations that are clonal/early events in the prostate cancer progression path, confirmed via chromoplexy analysis PMID:23622249
  • Heterozygous F133L hotspot mutation in MSK-PCa7; first in vitro prostate cancer model carrying this SPOP hotspot, enabling functional studies of this recurrent CRPC alteration PMID:25201530
  • SPOP mutated in 3/22 (14%) uterine/ovarian carcinosarcomas; missense mutations at E46K, E78K, M117V in/near the MATH domain PMID:25233892
  • SPOP is listed among candidate dark-matter driver genes in PTC; chromatin-remodeling/epigenetic regulator alterations spanning 93 mutations in 57 genes across 80/402 (20.0%) PTCs include SPOP as a putative driver requiring independent validation. PMID:25417114
  • AR pathway regulator mutated in metastatic castration-resistant prostate cancer (150-case WGS/WES cohort); part of the AR-pathway regulatory network alongside FOXA1, NCOR1, NCOR2. PMID:26000489
  • Hotspot mutations in 11% of primary prostate cancer (PRAD); mutually exclusive with ETS fusions; defines a subtype with CHD1 deletion, elevated methylation, SPINK1 overexpression, and highest AR transcriptional output PMID:26544944
  • Recurrent mCRPC driver mutation consistent with prior reports; identified among pan-metastasis driver genes in a rapid-autopsy whole-genome sequencing cohort PMID:26928463
  • Mutated in 14.3% of clear-cell endometrial carcinoma (CCEC; n=63) in a cross-histology endometrial sequencing study PMID:28485815
  • Enriched in earlier prostate cancer disease states (12% locoregional vs 5% mCRPC); paired with FOXA1, defines a possibly androgen-deprivation-sensitive subset (functional validation pending) PMID:28825054
  • Established prostate cancer driver confirmed in a 1,013-sample cohort; mutually exclusive with CUL3 mutations; both function in the BTB-CUL3-RBX1 E3 ubiquitin ligase complex. Metastasis-vs-primary enrichment quantified PMID:29610475

Cancer types (linked)

  • PRAD — mutations identified in PDX heterogeneity pair; SPOP is a canonical prostate adenocarcinoma driver PMID:38488813.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • No direct targeted therapy reported in the corpus.

Open questions

  • Functional validation of SPOP mutation effects in individual PDX models is not addressed in the corpus PMID:38488813.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22610119

This page was processed by crosslinker on 2026-05-14. - PMID:23622249

This page was processed by crosslinker on 2026-05-14. - PMID:25201530

This page was processed by crosslinker on 2026-05-14. - PMID:25233892

This page was processed by crosslinker on 2026-05-14. - PMID:25417114

This page was processed by crosslinker on 2026-05-14. - PMID:26000489

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14. - PMID:26928463

This page was processed by wiki-cli on 2026-05-14. - PMID:28485815

This page was processed by wiki-cli on 2026-05-15. - PMID:28825054

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

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