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

Breast Cancer Res Treat. 2009 Jan;113(2):285-91. doi: 10.1007/s10549-008-9942-3. Epub 2008 Feb 24.


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-Thr(68) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azacitidine / pharmacology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Line, Tumor / chemistry
  • Checkpoint Kinase 2
  • Codon, Nonsense
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • DNA Methylation
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Female
  • G1 Phase
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, cdc
  • Genes, p53
  • Humans
  • Male
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Tumor Suppressor Protein p53 / physiology


  • Codon, Nonsense
  • DNA, Neoplasm
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases
  • Azacitidine