{"entity":{"id":"paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019","kind":"paper","name":"Genomic correlates of clinical outcome in advanced prostate cancer","aka":[],"tldr":"Linking the genetics of 429 men with advanced prostate cancer to how long they lived showed that only one gene, RB1, predicted a worse outcome once everything else was accounted for.","summary":"Comprehensive genomic and transcriptomic analysis of 429 patients with metastatic castration-resistant prostate cancer was linked with longitudinal clinical outcomes, integrating whole-exome, transcriptome and histological analysis. For the 128 patients treated with a first-line next-generation androgen receptor signalling inhibitor, abiraterone or enzalutamide, the association of 18 recurrent DNA- and RNA-based alterations with clinical outcome was examined, including AR variant expression, AR transcriptional output and neuroendocrine expression signatures. Of these, only RB1 alteration was significantly associated with poor survival, whereas alterations in RB1, AR and TP53 were each associated with a shorter time on treatment with a receptor signalling inhibitor.","asOf":"2026-09-25","links":[{"label":"Abida et al., PNAS 2019: genomic correlates of clinical outcome in 429 patients with metastatic castration-resistant prostate cancer (SU2C/PCF)","url":"https://doi.org/10.1073/pnas.1902651116"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31061129/"},{"label":"cBioPortal study prad_su2c_2019 (SU2C/PCF Dream Team, PNAS 2019; 444 metastatic castration-resistant samples from 429 patients, whole exome)","url":"https://www.cbioportal.org/study/summary?id=prad_su2c_2019"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["rb1","androgen-receptor","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","p53-cell-cycle","lineage-plasticity-neuroendocrine"],"terms":["castration-resistance","resistance","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2019,"doi":"10.1073/pnas.1902651116","pmid":"31061129","authors":"Abida W, Cyrta J, Heller G, et al.","paperType":"observational","findings":["Only RB1 alteration was significantly associated with poor overall survival among 18 candidate markers.","RB1, AR and TP53 alterations each associated with shorter time on a first receptor signalling inhibitor.","A community resource pairing metastatic genomics with histology and longitudinal outcomes."],"whatItMeans":"It is the most disciplined outcome analysis in this disease and its result is deflationary in a useful way: most of the alterations people quote as prognostic do not survive adjustment, and the one that does, RB1, is also the one that marks the route to neuroendocrine transformation.","caveats":["Observational and not randomised, so the associations are prognostic rather than predictive.","One hundred and twenty-eight men in the treatment-outcome subset.","Academic referral centres, so the cohort is younger and fitter than the disease as a whole."],"changedPractice":false,"participants":429},"route":"/key-papers/paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019/","neighbours":{"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/"}],"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":"rb1","kind":"target","name":"RB1","route":"/targets/rb1/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"}],"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":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"}],"journal":[{"id":"pnas","kind":"journal","name":"Proceedings of the National Academy of Sciences","route":"/journals/pnas/"}]}}