Breast Cancer Research and Treatment

, Volume 113, Issue 2, pp 285–291

Deleterious CHEK2 1100delC and L303X mutants identified among 38 human breast cancer cell lines

  • Marijke Wasielewski
  • Pejman Hanifi-Moghaddam
  • Antoinette Hollestelle
  • Sofia D. Merajver
  • Ans van den Ouweland
  • Jan G. M. Klijn
  • Stephen P. Ethier
  • Mieke Schutte
Preclinical Study

Abstract

The CHEK2 protein plays a major role in the regulation of DNA damage response pathways. Mutations in the CHEK2 gene, in particular 1100delC, have been associated with increased cancer risks, but the precise function of CHEK2 mutations in carcinogenesis is not known. Human cancer cell lines with CHEK2 mutations are therefore of main interest. Here, we have sequenced 38 breast cancer cell lines for mutations in the CHEK2 gene and identified two cell lines with deleterious CHEK2 mutations. Cell line UACC812 has a nonsense truncating mutation in the CHEK2 kinase domain (L303X) and cell line SUM102PT has the well-known oncogenic CHEK2 1100delC founder mutation. Immunohistochemical analysis revealed that the two CHEK2 mutant cell lines expressed neither CHEK2 nor P-Thr68 CHEK2 proteins, implying abrogation of normal CHEK2 DNA repair functions. Cell lines UACC812 and SUM102PT thus are the first human CHEK2 null cell lines reported and should therefore be a major help in further unraveling the function of CHEK2 mutations in carcinogenesis.

Keywords

Cancer susceptibility Cell lines Gene mutation CHK2 p53 

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Marijke Wasielewski
    • 1
  • Pejman Hanifi-Moghaddam
    • 1
  • Antoinette Hollestelle
    • 1
  • Sofia D. Merajver
    • 2
  • Ans van den Ouweland
    • 3
  • Jan G. M. Klijn
    • 1
  • Stephen P. Ethier
    • 4
  • Mieke Schutte
    • 1
  1. 1.Department of Medical Oncology, Josephine Nefkens InstituteErasmus University Medical CenterRotterdamThe Netherlands
  2. 2.Department of Internal MedicineUniversity of Michigan Cancer CenterAnn ArborUSA
  3. 3.Department of Clinical GeneticsErasmus University Medical CenterRotterdamThe Netherlands
  4. 4.Barbara Ann Karmanos Cancer InstituteDetroitUSA

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