Master gene reprogramming and the development of prostate cancer

According to an hypothesis just published by a group of researchers at the Dana-Farber Cancer Institute in Boston, they have identified “a new epigenetic program occurring as you transition from normal to tumor cells” in the development of prostate cancer.

Their hypothesis is laid out in detail in a letter to the editor by Pomerantz et al. in Nature Genetics and in a media release issued by the Dana-Farber Cancer Institute. The full text of the letter to the editor in Nature Genetics is, unfortunately, not freely available on line. However, …

What Pomerantz and his colleagues are proposing, based on their findings to date, is that the development of prostate cancer (or at least some forms of prostate cancer) is initiated not as a consequence of a single mutation or a series of mutations in a patient’s DNA, but as a consequence of the reprogramming the master regulator of certain genes in prostate cells.   They argue that this hypothesis is supported by

  • Detailed evidence of cellular reprogramming when normal and cancerous prostate cells from several patients were compared
  • Clear evidence of “epigenetic” as opposed to purely genetic changes because their hypothesis explains the control over how genes in prostate and prostate cancer cells operate without permanent changes in their DNA code
  • Binding of androgen receptor-bound DNA of prostate cancer cells from prostate cancer patients to a different set of sites, or locks, than the ones it binds to in normal prostate cells.
  • Reprogramming of the androgen receptor to activate or deactivate genes in a way that spurred the prostate cells to grow and spread abnormally.

This is an extremely interesting hypothesis, that could not only offer us much greater insight into the development of rpostate cazncer in individual patients but also has significant potential with respect to the future diagnosis and management of prostate cancer. Could we identify such changes in the master gene programming accurately and early so as to diagnose prostate cancer early? Is the master gene programming reversible, in at least some patients?

Clearly this is only the beginning of another possible scientific pathway into the understanding and future medical management of prostate cancer, and there will be a long way to go before it can lead to practical medical applications for patients … but once again we should be “watching this space.”

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