{"entity":{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","aka":["TCGA prostate 2015","molecular taxonomy primary prostate cancer","seven subtypes prostate"],"tldr":"The Cancer Genome Atlas classified 333 prostate cancers taken out at surgery and found that three quarters fall into one of seven groups defined by a fusion or a mutation. A quarter had a change that a drug could in principle be aimed at, and one in five had a broken DNA repair gene.","summary":"The Cancer Genome Atlas Research Network profiled 333 primary prostate carcinomas across DNA, RNA, methylation and protein, and defined a taxonomy in which 74 percent of tumours belong to one of seven subtypes: the fusions ERG, ETV1, ETV4 and FLI1, and the mutations SPOP, FOXA1 and IDH1.\n\nAndrogen receptor activity varied widely and in a subtype-specific way, with SPOP and FOXA1 mutant tumours showing the highest androgen receptor-induced transcription. Twenty-five percent had a presumed actionable lesion in the PI3K or MAPK pathways, and DNA repair genes were inactivated in 19 percent, which is the finding that seeds the PARP inhibitor and platinum work in this disease. Roughly a quarter of primary prostate cancers still fall outside all seven subtypes, which is a candid statement of how much remains unclassified.","asOf":"2026-09-25","links":[{"label":"Cell 2015","url":"https://doi.org/10.1016/j.cell.2015.10.025"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26544944/"},{"label":"TCGA PRAD at the NCI Genomic Data Commons","url":"https://portal.gdc.cancer.gov/projects/TCGA-PRAD"},{"label":"cBioPortal study prad_tcga_pub (TCGA, Cell 2015; the 333 primary tumours of the published molecular taxonomy)","url":"https://www.cbioportal.org/study/summary?id=prad_tcga_pub"},{"label":"cBioPortal study prad_tcga_pan_can_atlas_2018 (TCGA PanCancer Atlas; 494 sequenced primary prostate adenocarcinomas, 489 with copy number, 494 with structural variants)","url":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018"}],"tags":["prostate-evidence"],"related":["paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","paper-taylor-integrative-genomic-profiling-cancer-cell-2010","paper-capitello-281-ann-oncol-2026","prostate-roadmap"],"cancers":["prostate","prostate-high-risk"],"sections":["diagnostics","targeted-therapy"],"technologies":["wes-wgs","rna-seq"],"targets":["spop","foxa1","erg","tmprss2","pten","pik3ca","androgen-receptor","brca","etv1","idh","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling","ar-signaling","pi3k-akt-mtor","ubiquitin-proteasome-system","epigenetic-reprogramming"],"terms":["hrd","ngs","gene-fusion","driver-mutation","gleason-grade-group","somatic-mutations-wxs-wgs"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-tumor-heterogeneity","b-data-silos"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2015,"doi":"10.1016/j.cell.2015.10.025","pmid":"26544944","authors":"Cancer Genome Atlas Research Network.","paperType":"basic","findings":["74 percent of 333 primary prostate carcinomas fell into one of seven subtypes defined by gene fusions (ERG, ETV1, ETV4, FLI1) or mutations (SPOP, FOXA1, IDH1).","Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype.","Androgen receptor activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumours having the highest levels of androgen receptor-induced transcripts.","25 percent of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signalling pathways.","DNA repair genes were inactivated in 19 percent of tumours."],"whatItMeans":"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.","caveats":["Primary tumours from men fit for radical prostatectomy, so it does not describe metastatic or castration-resistant disease; Robinson 2015 does that.","Presumed actionable is a bioinformatic judgement, not a demonstrated response to a drug.","26 percent of tumours fit none of the seven subtypes and remain unclassified."],"changedPractice":false,"participants":333},"route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/","neighbours":{"paper":[{"id":"paper-capitello-281-ann-oncol-2026","kind":"paper","name":"Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study","route":"/key-papers/paper-capitello-281-ann-oncol-2026/"},{"id":"paper-taylor-integrative-genomic-profiling-cancer-cell-2010","kind":"paper","name":"Integrative genomic profiling of human prostate cancer","route":"/key-papers/paper-taylor-integrative-genomic-profiling-cancer-cell-2010/"},{"id":"paper-tomlins-tmprss2-ets-fusion-science-2005","kind":"paper","name":"Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer","route":"/key-papers/paper-tomlins-tmprss2-ets-fusion-science-2005/"},{"id":"paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","route":"/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/"}],"roadmap":[{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"}],"cancer":[{"id":"prostate-high-risk","kind":"cancer","name":"Localised prostate cancer, high and very high risk","route":"/cancers/prostate-high-risk/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"erg","kind":"target","name":"ERG","route":"/targets/erg/"},{"id":"etv1","kind":"target","name":"ETV1","route":"/targets/etv1/"},{"id":"foxa1","kind":"target","name":"FOXA1","route":"/targets/foxa1/"},{"id":"idh","kind":"target","name":"IDH1 / IDH2","route":"/targets/idh/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"pten","kind":"target","name":"PTEN","route":"/targets/pten/"},{"id":"spop","kind":"target","name":"SPOP","route":"/targets/spop/"},{"id":"tmprss2","kind":"target","name":"TMPRSS2","route":"/targets/tmprss2/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"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":"gleason-grade-group","kind":"term","name":"Gleason score / Grade Group","route":"/terms/gleason-grade-group/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"somatic-mutations-wxs-wgs","kind":"term","name":"Somatic mutations from exome and genome sequencing (WXS, WGS)","route":"/terms/somatic-mutations-wxs-wgs/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-data-silos","kind":"bottleneck","name":"Data silos","route":"/bottlenecks/b-data-silos/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"journal":[{"id":"cell","kind":"journal","name":"Cell","route":"/journals/cell/"}],"biomarker":[{"id":"spop-mutation","kind":"biomarker","name":"SPOP mutation","route":"/biomarkers/spop-mutation/"},{"id":"tmprss2-erg-fusion","kind":"biomarker","name":"TMPRSS2-ERG fusion (and the other ETS rearrangements)","route":"/biomarkers/tmprss2-erg-fusion/"}]}}