{"entity":{"id":"paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","aka":["Robinson 2015","SU2C prostate 150 mCRPC","Stand Up To Cancer prostate dream team"],"tldr":"One hundred and fifty men with prostate cancer that had spread and stopped responding to hormones had their tumours biopsied and sequenced prospectively. Nine in ten had a genetic change that a drug could in principle be aimed at, and one in five had a broken DNA repair gene.","summary":"Dan Robinson, Arul Chinnaiyan, Charles Sawyers, Johann de Bono and the Stand Up To Cancer-Prostate Cancer Foundation Dream Team built a multi-institutional clinical sequencing infrastructure and prospectively whole-exome and transcriptome sequenced bone or soft tissue biopsies from 150 men with metastatic castration-resistant prostate cancer.\n\nThe single most consequential number is 19.3 percent: aberrations of BRCA2, BRCA1 and ATM at substantially higher frequency than in primary prostate cancer. That figure, together with Pritchard's germline result the following year, is why every man with metastatic prostate cancer should now be offered DNA repair testing. The paper also documented what castration resistance looks like at the genomic level: androgen receptor aberrations in 62.7 percent, and enrichment of TP53 and androgen receptor alterations relative to primary disease.","asOf":"2026-09-25","links":[{"label":"Cell 2015","url":"https://doi.org/10.1016/j.cell.2015.05.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26000489/"},{"label":"cBioPortal: SU2C/PCF prostate (2015)","url":"https://www.cbioportal.org/study/summary?id=prad_su2c_2015"}],"tags":["prostate-evidence"],"related":["paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["diagnostics","targeted-therapy"],"technologies":["wes-wgs","rna-seq","cgp"],"targets":["androgen-receptor","tp53","pten","brca","atm","pik3ca","erg","apc","zbtb16"],"drugs":[],"companies":[],"institutions":["michigan-rogel","mskcc","royal-marsden"],"pathways":["ar-signaling","homologous-recombination-repair","pi3k-akt-mtor","wnt","prostate-cancer-signalling"],"terms":["hrd","ngs","castration-resistance","germline-vs-somatic","driver-mutation","biopsy"],"trials":[],"people":["arul-chinnaiyan","charles-sawyers","johann-de-bono"],"bottlenecks":["b-biomarker-validation","b-hereditary-risk","b-data-silos"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2015,"doi":"10.1016/j.cell.2015.05.001","pmid":"26000489","authors":"Robinson D, Van Allen EM, Wu YM, et al.","paperType":"basic","findings":["Aberrations of the androgen receptor, ETS genes, TP53 and PTEN were frequent, in 40 to 60 percent of cases, with TP53 and androgen receptor alterations enriched in metastatic castration-resistant disease compared with primary prostate cancer.","Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies than in primary prostate cancers, at 19.3 percent overall.","89 percent of affected individuals harboured a clinically actionable aberration, including 62.7 percent with aberrations in the androgen receptor and 65 percent in other cancer-related genes.","8 percent had actionable pathogenic germline alterations.","New genomic alterations were identified in PIK3CA and PIK3CB, R-spondin, BRAF and RAF1, APC, beta-catenin and ZBTB16/PLZF."],"whatItMeans":"The genomic definition of advanced prostate cancer, and the evidence that made molecular testing standard in it. The 19.3 percent DNA repair figure is the direct ancestor of PROfound, TRITON3, PROpel and TALAPRO-2, and the 8 percent germline figure is why a tumour result in this disease has implications for a man's relatives.","caveats":["150 men who consented to a metastatic biopsy at academic centres, which selects for fitness and for accessible disease.","Clinically actionable was defined bioinformatically in 2015; most of the 89 percent had no drug available then and many still do not.","Bone biopsies yield lower tumour content than soft tissue, which affects detection sensitivity across the cohort unevenly."],"changedPractice":true,"participants":150},"route":"/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/","neighbours":{"paper":[{"id":"paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","kind":"paper","name":"Inherited DNA-repair gene mutations in men with metastatic prostate cancer","route":"/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/"},{"id":"paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","kind":"paper","name":"Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","route":"/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/"},{"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/"},{"id":"paper-grasso-mutational-landscape-lethal-crpc-nature-2012","kind":"paper","name":"The mutational landscape of lethal castration-resistant prostate cancer","route":"/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/"},{"id":"paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","kind":"paper","name":"TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer","route":"/key-papers/paper-mateo-toparp-a-olaparib-dna-repair-nejm-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-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"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":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"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":"apc","kind":"target","name":"APC","route":"/targets/apc/"},{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"erg","kind":"target","name":"ERG","route":"/targets/erg/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"pten","kind":"target","name":"PTEN","route":"/targets/pten/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"},{"id":"zbtb16","kind":"target","name":"ZBTB16","route":"/targets/zbtb16/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"royal-marsden","kind":"institution","name":"The Royal Marsden","route":"/institutions/royal-marsden/"},{"id":"michigan-rogel","kind":"institution","name":"University of Michigan Rogel Cancer Center","route":"/institutions/michigan-rogel/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"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":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"biopsy","kind":"term","name":"Biopsy","route":"/terms/biopsy/"},{"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":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"person":[{"id":"arul-chinnaiyan","kind":"person","name":"Arul M. Chinnaiyan","route":"/people/arul-chinnaiyan/"},{"id":"charles-sawyers","kind":"person","name":"Charles L. Sawyers","route":"/people/charles-sawyers/"},{"id":"johann-de-bono","kind":"person","name":"Johann de Bono","route":"/people/johann-de-bono/"}],"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-hereditary-risk","kind":"bottleneck","name":"Inherited risk is mostly unidentified","route":"/bottlenecks/b-hereditary-risk/"}],"journal":[{"id":"cell","kind":"journal","name":"Cell","route":"/journals/cell/"}],"idea":[{"id":"idea-prostate-hrr-testing-at-metastatic-diagnosis","kind":"idea","name":"Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later","route":"/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/"}],"biomarker":[{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"},{"id":"brca-somatic","kind":"biomarker","name":"Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations","route":"/biomarkers/brca-somatic/"}]}}