Analysis of KLLN as a high-penetrance breast cancer predisposition gene

Breast Cancer Res Treat. 2012 Jul;134(2):543-7. doi: 10.1007/s10549-012-2088-3. Epub 2012 May 13.

Abstract

KLLN is a p53 target gene with DNA binding function and represents a highly plausible candidate breast cancer predisposition gene. We screened for predisposing variants in 860 high-risk breast cancer families using high resolution melt analysis. A germline c.339_340delAG variant predicted to cause premature termination of the protein after 57 alternative amino acid residues was identified in 3/860 families who tested negative for BRCA1 and BRCA2 mutations and in 1/84 sporadic breast cancer cases. However, the variant was also detected in 2/182 families with known BRCA1 or BRCA2 mutations and in 2/464 non-cancer controls. Furthermore, loss of the mutant allele was detected in 2/2 breast tumors. Our data suggest that pathogenic mutations in KLLN are rare in breast cancer families and the c.339_340delAG variant does not represent a high-penetrance breast cancer risk allele.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation
  • Humans
  • Loss of Heterozygosity
  • Molecular Sequence Data
  • Penetrance*
  • Sequence Deletion
  • Tumor Suppressor Proteins / genetics*

Substances

  • KLLN protein, human
  • Tumor Suppressor Proteins