Microsatellite instability in radiation-induced murine tumours; Influence of tumour type and radiation quality

Jacqueline Haines*, Jeff Bacher, Margaret Coster, Rene Huiskamp, Emmy Meijne, Mariateresa Mancuso, Simonetta Pazzaglia, Simon Bouffler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Purpose:To investigate microsatellite instability (MSI) in radiation-induced murine tumours, its dependence on tissue (haemopoietic, intestinal, mammary, brain and skin) and radiation type. Materials and methods:DNA from spontaneous, X-ray or neutron-induced mouse tumours were used in Polymerase Chain Reactions (PCR) with mono-or di-nucleotide repeat markers. Deviations from expected allele size caused by insertion/deletion events were assessed by capillary electrophoresis. Results:Tumours showing MSI increased from 16 in spontaneously arising tumours to 23 (P0.014) in X-ray-induced tumours and rising again to 83 (P0.001) in neutron-induced tumours. X-ray-induced Acute Myeloid Leukaemias (AML) had a higher level of mono-nucleotide instability (45) than di-nucleotide instability (37). Fifty percent of neutron-induced tumours were classified as MSI-high for mono-nucleotide markers and 10 for di-nucleotide markers. Distribution of MSI varied in the different tumour types and did not appear random. Conclusions:Exposure to ionising radiation, especially neutrons, promotes the development of MSI in mouse tumours. MSI may therefore play a role in mouse radiation tumourigenesis, particularly following high Linear Energy Transfer (LET) exposures. MSI events, for a comparable panel of genome-wide markers in different tissue types, were not randomly distributed throughout the genome.

Original languageEnglish
Pages (from-to)555-568
Number of pages14
JournalInternational Journal of Radiation Biology
Volume86
Issue number7
DOIs
Publication statusPublished - Jul 2010

Bibliographical note

Funding Information:
We thank Neils De Wind (LUMC, Leiden) for the Msh27/7 cell line and Andrew Riches, Kazuko Yoshida for the AML cell lines. Paul Finnon, Naomi Robertson and Natalie Brown are thanked for their assistance with cell culture and isolation of clones and John Moody and Michele Ellender for providing DNA and tissue samples. This work was funded by EC RISC RAD contract FI6R-CT-2003-508842.

Keywords

  • X-rays
  • microsatellite instability
  • neutrons
  • tumours

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