New data on the genetics of aggressive prostate cancer, but …


A new paper in the Proceedings of the National Academy of Sciences suggests the existence of a subset of “hypermutated” cell lines in some forms of aggressive prostate cancer.

Kumar et al. carried out a series of sophisticated (“whole exome”) genetic sequencing studies on 23 cell lines derived from 16 different, lethal, metastatic prostate cancer tumors and three high-grade primary prostate cancer tumors. The full text of the paper is available on line for those with a detailed understanding of molecular genetics (or a strong sense of curiosity).

Basically, Kumar et al. were able to show the following:

  • Each tumor genome contained about 200 novel and non-synonymous gene variants.
  • Relatively few genes were mutated in the majority of tumor cell lines studied.
  • Most of these variants were specific to tumor lines from the cancers of specific individuals.
  • A few of the variants were commonly altered in tumors from different individuals.
  • Three of the prostate cancer genomes were “hypermutated,” with 2,000 to 4,000 novel coding variants.
  • Mutations in the so-called Wnt pathway may be particularly important to development of castration resistance.

Our ability to carry out these types of highly sophisticated genetic analysis continues to open doors to understanding about why some forms of prostate cancer are more aggressive than others. However, it is important to understand that there is a “chicken and the egg” effect going on in relation to these studies. We do not know how many of these genetic mutations may be a consequence of the development of prostate cancer or which ones may actually have a causative effect. It would be surprising if we were able to unravel this type of extraordinarily complex puzzle in the near future.

A more technical commentary on this paper that is may be “accessible” for some laypersons is available on the Genetic Engineering & Biotechnology News web site.

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