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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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Published on: September 20, 2016

Topoisomerase II gene mutations in tumors and tumor cell lines with microsatellite instability

Elena I Shagisultanova1, Zhe Piao, Hai-Ri Li

  • 1The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Cancer Letters
|November 10, 2004
PubMed

Insights

Microsatellite instability (MSI) drives cancer by causing mutations. This study found DNA topoisomerase II genes are mutated in 18% of MSI-positive cancers, suggesting TOPII modulation is key in MSI-positive cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Microsatellite mutator phenotype (MMP) or microsatellite instability (MSI) arises from DNA mismatch repair gene inactivation.
  • This phenotype promotes tumor development by causing mutations in cell growth and survival genes.

Purpose of the Study:

  • To investigate DNA topoisomerase II alpha (topIIalpha) and beta (topIIbeta) genes as potential mutational targets in MMP.
  • To determine the frequency of mutations in topIIalpha and topIIbeta in MSI-positive cancers.

Main Methods:

  • Screening of 10 MSI-positive human tumor cell lines and 30 MSI-positive colorectal tumors.
  • Analysis of mutations in the coding regions of topIIalpha and topIIbeta genes.

Main Results:

  • Mutations in topIIalpha or topIIbeta genes were identified in 18% of the samples analyzed.
  • Mutation frequency was 10% in primary colorectal tumors and 44% in cell lines.

Conclusions:

  • DNA topoisomerase II (TOPII) genes are frequently mutated in MSI-positive cancers.
  • Modulation of TOPII activity may play a significant role in the pathogenesis of MSI-positive cancer.

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