The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model

El Mustapha Bahassi, C. Gail Penner, Susan B. Robbins, Elisia Tichy, Estrella Feliciano, Moying Yin, Li Liang, Li Deng, Jay A. Tischfield, Peter J. Stambrook

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer and possibly other cancer types. In particular, the CHEK2*1100delC polymorphic variant has been identified as a low-penetrance breast cancer susceptibility allele in breast cancer families with wild type BRCA1 and BRCA2. To better understand the molecular basis by which this allele increases risk for disease, we have generated a mouse in which the wild type CHEK2 (Chk2 in mouse) allele has been replaced with the 1100delC variant. Mouse embryo fibroblasts (MEFs) derived from these mice have an altered cell cycle profile in which a far greater proportion of cells are in S-phase and in G2 (4N) compared with wild type cells. The mutant cells show signs of spontaneous genomic instability as indicated by polyploidy and an increase in DNA double strand breaks.

Original languageEnglish (US)
Pages (from-to)201-209
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume616
Issue number1-2
DOIs
StatePublished - Mar 1 2007

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Keywords

  • Breast cancer
  • CHEK2
  • DNA damage
  • Genomic instability
  • Mouse model

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