{"entity":{"id":"spop-mutation","kind":"biomarker","name":"SPOP mutation","aka":["SPOP","SPOP mutant","SPOP F133L","SPOP mutation","speckle-type POZ protein mutation"],"tldr":"The commonest single point mutation in prostate cancer, in about one tumour in eight. Tumours carrying it never have the usual ERG fusion, and men whose metastatic disease carries it tend to stay hormone-sensitive for longer.","summary":"Missense mutation in the substrate-binding cleft of SPOP, the adaptor of a cullin-3 ubiquitin ligase, found in 6 to 15% of tumours across multiple independent cohorts in the discovery paper and defining a molecular subtype that lacks ETS rearrangements (Barbieri 2012). Recomputed on cBioPortal: 318 of 2,260 (14.1%) in prostate_msk_2024, 260 of 2,069 (12.6%) in prad_msk_stopsack_2021, 55 of 494 (11.1%) in prad_tcga_pan_can_atlas_2018, 53 of 424 (12.5%) in prad_mcspc_mskcc_2020 and 25 of 444 (5.6%) in prad_su2c_2019. The mutations are tightly clustered: of 325 mutation records in prostate_msk_2024, F133L accounts for 66, F133V 43, F102C 33, F102V 22, W131G 20, Y87N 14 and Y87C 14. With FOXA1-mutant tumours, SPOP-mutant tumours carry the highest androgen receptor transcriptional output of the seven TCGA classes (Cancer Genome Atlas Research Network 2015). In 424 men with metastatic castration-sensitive disease, SPOP alteration was associated with a lower rate of castration resistance and longer overall survival, adjusting for disease volume and other pathways (Stopsack 2020).","asOf":"2026-09-25","links":[{"label":"Barbieri et al., Nat Genet 2012: exome sequencing of 112 prostate tumour and normal pairs identifies recurrent SPOP, FOXA1 and MED12 mutations","url":"https://doi.org/10.1038/ng.2279"},{"label":"Stopsack et al., Clin Cancer Res 2020: oncogenic alterations, phenotypes and outcomes in 424 men with metastatic castration-sensitive prostate cancer","url":"https://doi.org/10.1158/1078-0432.CCR-20-0168"},{"label":"cBioPortal study prostate_msk_2024 (MSK-IMPACT, Clin Cancer Res 2024; 2,260 prostate cancers, the largest panel cohort, primary and metastatic)","url":"https://www.cbioportal.org/study/summary?id=prostate_msk_2024"}],"tags":["biomarker","prostate"],"related":["tmprss2-erg-fusion"],"cancers":["prostate","prostate-mhspc"],"sections":[],"technologies":["cgp"],"targets":["spop","androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["ubiquitin-proteasome-system","ar-signaling","prostate-cancer-signalling"],"terms":["driver-mutation","gene-fusion","castration-resistance","mcrpc-mhspc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012","paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020"],"journals":[],"dependsOn":[],"notes":[],"target":"spop","measurement":"sequencing-variant","scoringRule":{"text":"A missense mutation in the SPOP substrate-binding cleft, most often at F133, F102, W131 or Y87, on tumour sequencing. It is mutually exclusive with ETS rearrangement, so a tumour reported as both should prompt a check.","quote":"SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across multiple independent cohorts.","source":"https://doi.org/10.1038/ng.2279","sourceLabel":"Barbieri et al., Nature Genetics 2012"},"thresholds":[],"definedBy":{"label":"Stopsack et al., Clin Cancer Res 2020: oncogenic alterations and outcomes in 424 men with metastatic castration-sensitive prostate cancer","url":"https://doi.org/10.1158/1078-0432.CCR-20-0168"},"tests":[],"assays":[],"companionDiagnostics":[],"forPatient":"No treatment is chosen because of this result, and on the evidence so far it is a favourable one: men whose metastatic prostate cancer carries it tend to respond to hormone treatment for longer. It is a description of the kind of prostate cancer you have rather than an instruction."},"route":"/biomarkers/spop-mutation/","neighbours":{"biomarker":[{"id":"tmprss2-erg-fusion","kind":"biomarker","name":"TMPRSS2-ERG fusion (and the other ETS rearrangements)","route":"/biomarkers/tmprss2-erg-fusion/"}],"cancer":[{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"spop","kind":"target","name":"SPOP","route":"/targets/spop/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"prostate-cancer-signalling","kind":"pathway","name":"Prostate cancer (KEGG map)","route":"/pathways/prostate-cancer-signalling/"},{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}],"term":[{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","route":"/terms/mcrpc-mhspc/"}],"paper":[{"id":"paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012","kind":"paper","name":"Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer","route":"/key-papers/paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012/"},{"id":"paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020","kind":"paper","name":"Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer","route":"/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"}]}}