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The first large look at prostate cancer across copy number, gene expression and sequence at once. Its most useful finding for patients was that the pattern of gained and lost chromosome segments separates low-risk from high-risk disease better than the Gleason score does.
Barry Taylor, Charles Sawyers, William Gerald and colleagues at Memorial Sloan Kettering assessed DNA copy number, messenger RNA expression and focused exon resequencing concordantly in 218 prostate tumours, and released the genomic and clinical outcome data as a public resource.
Two results stand out. NCOA2, a nuclear receptor coactivator, behaved as an oncogene in around 11 percent of tumours, extending the androgen receptor pathway beyond the receptor itself. And copy-number alterations in primary tumours defined clusters of low-risk and high-risk disease beyond what the Gleason score achieved, which is the intellectual origin of the commercial genomic classifiers now used to decide who needs radical treatment.
The origin of the idea that a prostate tumour's copy-number pattern carries prognostic information the pathologist's grade does not. That idea became Decipher and the other genomic classifiers, which are now used in some systems to decide whether a man needs radiotherapy after surgery.
One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
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.
The most common single molecular event in prostate cancer, present in roughly half of tumours in most series, and the reason prostate cancer is classified by fusion status. It is also a standing reminder that finding the driver and drugging it are different problems: no ETS-directed therapy has reached the clinic.
Shares TMPRSS2, The mutational landscape of lethal castration-resistant prostate cancer, ERG, Localised prostate cancer, high and very high risk and the tag prostate-evidence.
Shares Charles L. Sawyers, The mutational landscape of lethal castration-resistant prostate cancer, TCGA: the molecular taxonomy of primary prostate cancer, ERG and the tag prostate-evidence.
Shares TMPRSS2, ERG, Next-generation sequencing (NGS), 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 and the tag prostate-evidence.
Shares Charles L. Sawyers, Tumour heterogeneity and clonal evolution, 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, Androgen receptor and the tag prostate-evidence.
Shares Gleason score / Grade Group, Localised prostate cancer, high and very high risk, 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, Biomarkers are not validated or standardised and the tag prostate-evidence.
Shares Tumour heterogeneity and clonal evolution, 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, Androgen receptor, Prostate cancer and the tag prostate-evidence.
Shares Gleason score / Grade Group, Localised prostate cancer, high and very high risk, 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, Biomarkers are not validated or standardised and the tag prostate-evidence.
Shares Charles L. Sawyers, 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, Androgen receptor, Prostate cancer and the tag prostate-evidence.