Mutational analysis of the TrkA gene in prostate cancer

Daniel J. George, Hiroyoshi Suzuki, G. Steven Bova, John T. Isaacs

Research output: Contribution to journalArticlepeer-review

Abstract

BACKROUND. TrkA, the high affinity, tyrosine kinase receptor for nerve growth factor (NGF) has been implicated as an oncogene in several neoplasms. In prostate cancer, inhibitors of the NGF/TrkA signal pathway results in tumor growth inhibition. In contrast, inhibition of this trk pathway in the normal prostate produces no effect. One explanation for this difference between normal and malignant prostate is that TrkA is mutated in prostate cancer, changing its function. To test this possibility human primary prostate cancers were screened for evidence of mutations in the TrkA gene to identify how this gene might be activated in prostate cancer. METHODS. Single-strand conformation polymorphism was used to screen genomic DNA, isolated from 42 human primary prostate cancers. In samples in which an aberrant banding pattern was identified, the screen was repeated using both the tumor DNA and DNA isolated from normal tissue of the same patients. Genetic changes were confirmed by direct sequencing of the aberrantly migrating bands. RESULTS. Although somatic mutations were not identified in any of the exons screened, four polymorphisms were detected in three different exons. Some of these polymorphisms occurred in the majority of the patients screened, but their frequencies were similar when compared with DNA isolated from a control group. CONCLUSIONS. Genetic mutations of TrkA do not seem to play a significant role in activation of this pathway in prostate cancer. However, the absence of mutations in otherwise genetically unstable prostate tumor DNA suggests that intact NGF/TrkA pathways may be important in prostate cancer development.

Original languageEnglish (US)
Pages (from-to)172-180
Number of pages9
JournalProstate
Volume36
Issue number3
DOIs
StatePublished - Aug 1 1998

Keywords

  • Prostate cancer
  • Single-strand conformation polymorphism
  • TrkA

ASJC Scopus subject areas

  • Oncology
  • Urology

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