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Reanalysing 1,013 prostate cancers the same way found 97 genes driving the disease, 70 of them new, and almost all of them mutated in fewer than three tumours in a hundred.
Exome sequencing data from 1,013 prostate cancers were aggregated and uniformly analysed. A new class of ETS fusion-negative tumours was identified and validated, defined by mutations in epigenetic regulators, alongside alterations in pathways not previously implicated in prostate cancer such as the spliceosome pathway. The incidence of significantly mutated genes followed a long-tail distribution, with many genes mutated in less than 3% of cases. Ninety-seven significantly mutated genes were identified in total, including 70 not previously implicated in prostate cancer, among them the ubiquitin ligase CUL3 and the transcription factor SPEN. Comparing primary and metastatic prostate cancer identified genomic markers that may inform risk stratification.
It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.
Shares FOXA1, SPOP, Somatic mutations from exome and genome sequencing (WXS, WGS), ERG.
Shares FOXA1, KMT2C, KMT2D, Somatic mutations from exome and genome sequencing (WXS, WGS).
Shares FOXA1, SPOP, Somatic mutations from exome and genome sequencing (WXS, WGS), ERG.
Shares SPOP, Ubiquitin-proteasome system & protein homeostasis, Prostate cancer (KEGG map), Gene fusion.
Shares ERG, Prostate cancer (KEGG map), Gene fusion, Driver mutation.
Shares KMT2D, Somatic mutations from exome and genome sequencing (WXS, WGS), Nature Genetics, Driver mutation.
Shares FOXA1, Prostate cancer (KEGG map), Driver mutation, Prostate cancer.
Shares ERG, Prostate cancer (KEGG map), Gene fusion, Prostate cancer.