Microsatellite mutation (CAG24→18) in the androgen receptor gene in human prostate cancer

Mark P. Schoenberg, Janette M. Hakimi, Suping Wang, G. Steven Bova, Jonathan I. Epstein, Kenneth H. Fischbeck, William B. Isaacs, Patrick C. Walsh, Evelyn R. Barrack

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

The androgen receptor (AR) gene contains a polymorphic CAG microsatellite that codes for a variable length of glutamine repeats in the AR protein. Microsatellite DNA sequences may be potential sites of genetic instability. Using the polymerase chain reaction (PCR), we screened 40 human prostate cancer specimens for expansions or deletions of this microsatellite. In one patient, nontumor DNA yielded a single PCR product, as expected for the AR, but the tumor DNA yielded two discrete products, one identical to normal, and a second smaller one. Direct sequencing revealed that the nontumor tissue contained 24 CAGs, whereas the tumor contained one fragment with 24 CAGs (wild-type) and a second fragment with 18 CAGs (mutant), representing a somatic contraction of the AR CAG repeat (CAG24→CAG18) in the tumor. Interestingly, this patient manifested a paradoxical agonistic response to hormonal therapy with the antiandrogen flutamide.

Original languageEnglish (US)
Pages (from-to)74-80
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume198
Issue number1
DOIs
StatePublished - Jan 15 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Schoenberg, M. P., Hakimi, J. M., Wang, S., Bova, G. S., Epstein, J. I., Fischbeck, K. H., Isaacs, W. B., Walsh, P. C., & Barrack, E. R. (1994). Microsatellite mutation (CAG24→18) in the androgen receptor gene in human prostate cancer. Biochemical and Biophysical Research Communications, 198(1), 74-80. https://doi.org/10.1006/bbrc.1994.1011