Tissue Sources for Accurate Measurement of Germline DNA Genotypes in Prostate Cancer Patients Treated With Radical Prostatectomy

Prostate. 2017 Mar;77(4):425-434. doi: 10.1002/pros.23283. Epub 2016 Nov 30.

Abstract

Background: Benign tissue from a tumor-containing organ is commonly the only available source for obtaining a patient's unmutated genome for use in cancer research. While it is critical to identify histologically normal tissue that is independent of the tumor lineage, few additional considerations are applied to the choice of this material for such measurements.

Methods: Normal formalin-fixed, paraffin-embedded seminal vesicle, and urethral tissues, in addition to whole blood, were collected from 31 prostate cancer patients having undergone radical prostatectomy. Genotype concordance was evaluated for DNA from each tissue source in relation to whole blood.

Results: Overall, there was a greater genotype call rate for DNA derived from urethral tissue (97.0%) in comparison with patient-matched seminal vesicle tissues (95.9%, P = 0.0015). Furthermore, with reference to patient-matched whole blood, urethral samples exhibited higher genotype concordance (94.1%) than that of seminal vesicle samples (92.5%, P = 0.035).

Conclusions: These findings highlight the heterogeneity between diverse sources of DNA in genotype measurement and motivate the consideration of normal tissue biases in tumor-normal analyses. Prostate 77: 425-434, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: archival FFPE tissue; genotype concordance; seminal vesicle; tumor-normal; urethra.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Germline Stem Cells / physiology
  • Aged
  • DNA / genetics*
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Prostatectomy / standards*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / surgery*
  • Seminal Vesicles / pathology
  • Seminal Vesicles / physiology
  • Seminal Vesicles / surgery
  • Treatment Outcome
  • Urethra / pathology
  • Urethra / physiology
  • Urethra / surgery

Substances

  • DNA