Microsatellite instability and mismatch repair target gene mutations in cell lines and xenografts of prostate cancer

Prostate. 2006 May 1;66(6):660-6. doi: 10.1002/pros.20390.

Abstract

Background: Mismatch repair (MMR) and microsatellite instability (MSI) occur in prostate cancer, but their role has not been well documented.

Methods: In 6 cell lines and 22 xenografts from prostate cancer, PCR and gel electrophoresis were performed to detect MSI by analyzing microsatellite markers BAT-25 and BAT-26 and to detect frameshift mutations in mononucleotide repeats in BAX, IGF2R, MSH3, MSH6, and TGFBR2.

Results: Four of 6 (67%) cell lines and 3 of 22 (14%) xenografts showed MSI. At least 1 frameshift mutation was detected in the same 4 (67%) cell lines and in 5 of 22 (23%) xenografts. While MSH3 was frequently mutated in cell lines, BAX and TGFBR2 showed frequent alterations in both cell lines and xenografts.

Conclusions: MSI related to MMR deficiency is relatively frequent in high-grade tumors, and mutations in MSI target genes involved in cell death and proliferation appeared to be selected for during prostatic carcinogenesis.

Publication types

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

MeSH terms

  • Animals
  • Base Pair Mismatch*
  • Cell Line, Tumor
  • DNA Primers
  • Humans
  • Male
  • Microsatellite Repeats / genetics*
  • Mutation*
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / genetics*
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Transplantation, Heterologous
  • bcl-2-Associated X Protein / genetics

Substances

  • DNA Primers
  • Receptors, Transforming Growth Factor beta
  • bcl-2-Associated X Protein
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II