Gene copy number alteration analysis and risk for prostate cancer-specific mortality


A new study, to published shortly on-line in Cancer, suggests that significant alterations to the “copy numbers” of the PTEN and MYC genes in men with prostate cancer are strongly associated with risk for prostate cancer-specific mortality.

This paper by Liu et al. looked initially at data from the DNA of tumors in 125 men who had radical prostatectomies for initial treatment of prostate cancer. Based on these data, the authors were able to show the following:

  • There were 20 significant regions of gene copy number alterations (CNAs).
  • 4/20 of these genetic CNAs were novel, and could be used to identify the relevant target genes.
  • 7/20 of the genetic CNAs were significantly associated with early prostate cancer-specific mortality.
  • On multivariate analysis, however,
    • Only the CNAs of the PTEN (phosphatase and tensin homolog) and MYC (v-myc myelocytomatosis viral oncogene homolog) genes contributed additional prognostic information independent of the prognostic information already available (i.e., pathologic stage, Gleason score, and initial PSA level).
    • Patients whose tumors had CNAs of both genes had a markedly elevated risk of prostate cancer-specific mortality (odds ratio [OR] = 53)

Liu et al. then went on to confirm the relationship between the CNAs of PTEN and MYC by analyzing the DNA from 333 further tumors from patients in three more distinct cohorts of men.

The authors conclude that “CNA profiles in biopsy samples could help select those patients best treated with prostatectomy or radiation and those who could be managed conservatively.” Dr. Liu is quoted as stating in an associated media release that:

… prostate cancer patients who have DNA copy number alterations at PTEN and MYC may not be appropriate candidates for active surveillance and should be treated intensively.

While this is certainly true, we clearly are going to need to be able to conduct such gene CNA analysis with a very high degree of efficiency before this could become a routine aspect of the work-up of patients with an initial diagnosis of prostate cancer.

3 Responses

  1. That is great news. If it holds up it will make deciding whether or not to have surgery a much easier decision.

  2. USE IN RESEARCH AS WELL AS IN TREATMENT DECISION MAKING

    What a great development! That odds ratio of 53 is awesome!

    If cost is affordable for trials, staging patients for these two copy number altertions would appear to have potential for bringing results of trials into much clearer focus.

    Would it not also be feasible to stage tissue samples for patients in many key past trials to retrospectively refine findings? As an example, I’m trying to visualize how such information could be applied to men in the PLCO and ERSPC trials.

    What additional confirmation is needed before this technology would be ready for prime time?

  3. Jim:

    (1) This work needs to be replicated by an independent laboratory (as in “one swallow does not a summer make”).

    (2) The methodology would need to be standardized to make sure one was comparing apples to apples.

    (3) Then there would be the cost issue … and I don’t think this is low-cost!

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