{"entity":{"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","aka":[],"tldr":"Sequencing the genes of 112 prostate cancers found the disease's commonest point mutation in a gene nobody had linked to it, and showed those tumours are a separate kind that never carries the usual fusion.","summary":"The exomes of 112 prostate tumour and normal tissue pairs were sequenced. New recurrent mutations were identified in multiple genes including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6 to 15% of tumours across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations, so SPOP mutation appears to define a molecular subtype.","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":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22610119/"},{"label":"cBioPortal study prad_broad (Broad and Cornell, Nat Genet 2012; 112 sequenced primary tumour and normal pairs)","url":"https://www.cbioportal.org/study/summary?id=prad_broad"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["wes-wgs"],"targets":["spop","foxa1","erg"],"drugs":[],"companies":[],"institutions":[],"pathways":["ubiquitin-proteasome-system","prostate-cancer-signalling","ar-signaling"],"terms":["driver-mutation","gene-fusion","somatic-mutations-wxs-wgs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2012,"doi":"10.1038/ng.2279","pmid":"22610119","authors":"Barbieri CE, Baca SC, Lawrence MS, et al.","paperType":"basic","findings":["SPOP the most frequently mutated gene, in 6 to 15% of tumours across independent cohorts.","Mutations cluster in the substrate-binding cleft of the SPOP protein.","SPOP-mutant tumours lack ETS rearrangements and carry their own copy-number pattern.","New recurrent mutations in FOXA1 and MED12."],"whatItMeans":"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.","caveats":["One hundred and twelve exomes, so rarer events were missed; the 1,013-exome reanalysis later found a long tail.","No SPOP-directed medicine exists.","Localised disease, so the mutation frequencies in metastatic disease are different."],"changedPractice":false,"participants":112},"route":"/key-papers/paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012/","neighbours":{"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"erg","kind":"target","name":"ERG","route":"/targets/erg/"},{"id":"foxa1","kind":"target","name":"FOXA1","route":"/targets/foxa1/"},{"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":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"somatic-mutations-wxs-wgs","kind":"term","name":"Somatic mutations from exome and genome sequencing (WXS, WGS)","route":"/terms/somatic-mutations-wxs-wgs/"}],"journal":[{"id":"nature-genetics","kind":"journal","name":"Nature Genetics","route":"/journals/nature-genetics/"}],"biomarker":[{"id":"spop-mutation","kind":"biomarker","name":"SPOP mutation","route":"/biomarkers/spop-mutation/"}]}}