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The largest routine-practice picture of what is broken in prostate tumours. Across 3,476 samples sent for commercial sequencing, TP53 was altered in 44 percent and PTEN in 32 percent, and just over half carried something a drug is being developed against.
Jon Chung, Jeffrey Ross and colleagues at Foundation Medicine analysed 3,476 clinically advanced prostate tumours sent for comprehensive genomic profiling, 1,660 from primary sites and 1,816 from metastases in unmatched patients, and reported both gene-level alterations and genome-wide signatures: loss of heterozygosity, microsatellite instability and tumour mutational burden.
This is the real-world counterpart to TCGA and the SU2C cohort, and it is the right citation for what a clinician actually sees on a report. It also makes two points the research cohorts do not. Median tumour mutational burden is low at 2.6 mutations per megabase and only 3 percent of tumours are high, of which 71 percent are also microsatellite-unstable, which is why immunotherapy fails in this disease. And CDK12-altered tumours, unlike BRCA and ATR-altered ones, are infrequently high for genome-wide loss of heterozygosity, so they are not homologous recombination deficient in the sense PARP inhibitors need.
What a prostate cancer sequencing report looks like in practice, and the numerical basis for two clinical rules: do not expect checkpoint immunotherapy to work unless the tumour is mismatch repair deficient, and do not treat a CDK12 alteration as if it were a BRCA alteration.
This is the paper Europe PMC returns for registry id NCT03748641 with the most citations, so it is the natural first reading for anyone following the MAGNITUDE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
The measured size of the immunotherapy problem in prostate cancer: a response rate in the low single figures, no signal from PD-L1 expression, and durable benefit in a small subgroup nobody can yet identify prospectively. Any claim that immunotherapy is coming to prostate cancer has to explain this trial.
Shares TMPRSS2, ERG, SU2C-PCF: integrative clinical genomics of advanced prostate cancer, PTEN and the tag prostate-evidence.
Shares TMPRSS2, Chromoplexy, ERG, SU2C-PCF: integrative clinical genomics of advanced prostate cancer and the tag prostate-evidence.
Shares TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer, SU2C-PCF: integrative clinical genomics of advanced prostate cancer, Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later, Homologous recombination deficiency (HRD) and the tag prostate-evidence.
Shares TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer, Genome-wide loss of heterozygosity (gLOH), Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later, Homologous recombination deficiency (HRD) 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 TMPRSS2, Chromoplexy, ERG, Next-generation sequencing (NGS) and the tag prostate-evidence.
Shares SU2C-PCF: integrative clinical genomics of advanced prostate cancer, Homologous recombination deficiency (HRD), 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 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.