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

Marijke Wasielewski (1) , Pejman Hanifi-Moghaddam (1) , Antoinette Hollestelle (1) , Sofia D. Merajver (2) , Ans Ouweland (3) , Jan G. M. Klijn (1) , Stephen P. Ethier (4) , Mieke Schutte (1)

1 Department of Medical Oncology, Josephine Nefkens Institute
2 Department of Internal Medicine
3 DCG - Department of Clinical Genetics
4 Barbara Ann Karmanos Cancer Institute

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

Mots clés: Cancer susceptibility; Cell lines; Gene mutation

Marijke Wasielewski, Pejman Hanifi-Moghaddam, Antoinette Hollestelle, Sofia D. Merajver, Ans Ouweland, et al.. Deleterious 1100delC and L303X mutants identified among 38 human breast cancer cell lines. Breast Cancer Research and Treatment, 2008, 113 (2), pp.285-291. ⟨10.1007/s10549-008-9942-3⟩. ⟨hal-00478318⟩