Many years ago (in late 1995 I believe), relatively soon after we had started the original version of this web service, I was contacted by Dr. Steven Bova from Johns Hopkins. He was trying to identify living prostate cancer patients willing to donate their bodies to research at the time of their deaths. The core results of this research project were published last week in Nature Medicine.
The paper by Liu et al. uses data from highly detailed autopsies of 33 prostate cancer patients to show that most, if not all, metastatic prostate cancers “have monoclonal origins and maintain a unique signature copy number pattern of the parent cancer cell while also accumulating a variable number of separate subclonally sustained changes.” In plain English, most metastatic prostate cancers can be traced to a mutation in a single prostate cancer cell.
A report about this study on Biology News Net quotes Dr. Bova extensively. The key point that Dr. Bova makes in this interview is that although the exact location of the DNA mutation was different for each patient studied, all the mutations seem to have occurred in the same general region of their DNA. This finding should be of considerable value in helping to narrow the focus of research into the underlying causes of prostate cancer and guide personalized cancer therapy.
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Re: monoclonal origin of prostate cancer — What implications, if any, are there on the status of the Gleason grade for cancers of monoclonal origin?
Is the Gleason grade of a cancer determined by the original source cells and remain the same as those cells multiply, or do the cells in the cancer from a given origin become more poorly differentiated as the cancer spreads (i.e., Gleason grade increases for a family of cells derived from an original cancer cell)?
Dear Jon: This may not be a cell-specific issue. Gleason grades are based on the appearance of relatively large groups of cells, not the individual cells.
Despite a monoclonal origin, it is probable that the way a cancer progresses is dependent on the environment of the cell in a particular human as well as on the initial mutation.
So, for example, if I normally have lower testosterone levels than you do, but we both started with a single identical prostate cancer cell, my cancer might grow faster (or slower) than yours, and change into a more (or less) aggressive form of cancer. In other words, knowing whether a cancer is monoclonal or not may not be the only relevant issue, although the nature of the initial, underlying mutation is certainly likely to be important.