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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.
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).
In plain words · SPOP (Speckle-type POZ protein) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Prostate cancer, Endometrial cancer, Non-Hodgkin lymphoma and 4 more.
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.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
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.
“SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across multiple independent cohorts.”
Barbieri et al., Nature Genetics 2012No approval uses this readout as a threshold. It is defined by Stopsack et al., Clin Cancer Res 2020: oncogenic alterations and outcomes in 424 men with metastatic castration-sensitive prostate cancer.
It fills the gap between the primary-tumour atlases and the castration-resistant series by describing the disease at the moment most treatment decisions are actually made, and it identifies SPOP as a favourable marker rather than a neutral one.
The reference classification of prostate cancer as it presents, and the source of the two numbers that drive most molecular treatment decisions in the disease: a quarter with a PI3K or MAPK lesion, which is the rationale for capivasertib in PTEN-deficient disease, and a fifth with DNA repair inactivation, which is the rationale for PARP inhibitors.
It established the fusion-negative side of the prostate cancer taxonomy and made SPOP the disease's signature point mutation, in a ubiquitin ligase adaptor rather than in a kinase, which is part of why prostate cancer has so few druggable drivers.
Shares Androgen receptor, Comprehensive genomic profiling, Prostate cancer and the tags biomarker, prostate.
Shares Metastatic hormone-sensitive prostate cancer, Castration-resistant prostate cancer (CRPC), Comprehensive genomic profiling, Prostate cancer and the tags biomarker, prostate.
Shares Androgen receptor, Prostate cancer and the tags biomarker, prostate.
Shares Prostate cancer (KEGG map), Androgen receptor signalling, Metastatic hormone-sensitive prostate cancer, Castration-resistant prostate cancer (CRPC) and the tag biomarker.
Shares Androgen receptor signalling, Driver mutation, Castration-resistant prostate cancer (CRPC), Androgen receptor and the tag biomarker.
Shares TMPRSS2-ERG fusion (and the other ETS rearrangements), Prostate cancer (KEGG map), Androgen receptor signalling, Gene fusion.
Shares Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Androgen receptor, Comprehensive genomic profiling and the tag biomarker.
Shares Metastatic hormone-sensitive prostate cancer, Prostate cancer and the tag prostate.