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Gene fusions were thought to be a feature of leukaemias, not common solid cancers. This study found one in prostate cancer that joins a switch controlled by testosterone to a growth gene, and found it in most of the tumours it looked at.
Scott Tomlins, Arul Chinnaiyan and colleagues at Michigan used a bioinformatics method that looks for genes expressed at extreme levels in a minority of samples, identified ERG and ETV1 as outliers in prostate cancer, and then found recurrent fusions joining the 5 prime untranslated region of TMPRSS2 to one or the other.
The mechanism is elegant and specifically prostatic: TMPRSS2 is androgen-responsive, so the fusion puts an ETS transcription factor under the control of the hormone that the prostate is bathed in. It was the first recurrent chromosomal rearrangement found in a common carcinoma, and it broke the assumption that fusions belong to haematological cancers. Twenty years later it defines the largest molecular subtype of prostate cancer and has still produced no drug, which is the honest state of the finding.
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 Arul M. Chinnaiyan, TMPRSS2, University of Michigan Rogel Cancer Center, ERG and the tag prostate-evidence.
Shares Arul M. Chinnaiyan, University of Michigan Rogel Cancer Center, ERG, TCGA: the molecular taxonomy of primary prostate cancer and the tag prostate-evidence.
Shares TMPRSS2, ERG, Localised prostate cancer, high and very high risk, Next-generation sequencing (NGS) and the tag prostate-evidence.
Shares Cytogenetics and FISH, Prostate cancer (KEGG map), Androgen receptor signalling, 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.
Shares Science, Androgen receptor signalling, The undruggable drivers, 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 The undruggable drivers, 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, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares Transcriptional machinery & addiction, Androgen receptor signalling, 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.