DNA methylation and the aggressiveness of prostate cancer


According to a media release from the Mayo Clinic earlier today, “Alterations to the ‘on-off’ switches of genes occur early in the development of prostate cancer and could be used as biomarkers to detect the disease months or even years earlier than current approaches.”

The relevant research paper has — supposedly —  just been published on line in the journal Clinical Cancer Research, and of course the first critical question it raises is whether the ability to use the relevant biomarkers (DNA methylation profiles) can help us to distinguish with accuracy between cancers that are indolent and which will never need treatment and cancers which have the potential to metastasize. Alas, as yet there is no sign of the abstract of the paper on the web site of the journal!

There is more information in the full text of the media release, and there is also more information on excerpts from video interviews with some of the authors on the Mayo Clinical News Network (but you have to be approved to have access to these interviews), so for the time being we are limited to the media release.

According to this release:

  • The authors studied the DNA methylation profiles of 14,495 genes from prostate cancers in 238 patients, including
    • Genes from men whose cancer never recurred after first-line treatment
    • Genes from men whose cancer recurred locally after first-line treatment
    • Genes from men whose cancer metastasized
  • DNA methylation changes observed during the earliest stages of prostate cancer development were nearly identical in all patients.
  • The authors identified “distinct” alterations in patterns of DNA methylation that could be used to distinguish between indolent and more aggressive tumors.

The senior author, Krishna Donenka, PhD, is quoted as saying that, “Our approach is more accurate and reliable than the widely used PSA … test,” but then any new test had better be significantly better that the current PSA test, so that’s only step one toward a test that can really revolutionize the diagnosis and management of prostate cancer.

At least DNA methylation change would be prostate cancer specific — which of course the PSA test is not.

DNA methylation of specific genes is an increasingly well-understood process by which the body controls whether particular genes are turned “off” or turned “on” at a particular point in time. It is not the only process that affects the degree of expression of a particular gene — but it is very certainly an important one.

2 Responses

  1. Dear Sitemaster,

    Can you give me a good reference on gene expression and cancer in general, or prostate cancer in particular? A microbiologist here recently told me a bit about epigenetic research, and I have seen a few short articles in New Scientist. My interest in this concerns pure science, not my case of prostate cancer. Even before I heard about epigenetic phenomena, I saw little reason why the “central dogma” of genetic biology should be fully true. It helped in the initial stages of research, but I could not fully believe that there’s no “two-way traffic” of chemical and/or other influences on the contents of the cell nucleus.

  2. George:

    Off the top of my head, I am really not aware of “one good reference” on this topic (although there might be three or four articles in Scientific American over the past 3 or 4 years that would give you a good grounding. I will see if I can look around later this week. I’m kinda tied up today and tomorrow.

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