title: Analysis of KLLN as a high-penetrance breast cancer predisposition gene.
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.
authors.affiliation: VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, East Melbourne, VIC 8006, Australia.
authors.forename: Ella R
authors.initials: ER
authors.lastname: Thompson
authors.forename: Kylie L
authors.initials: KL
authors.lastname: Gorringe
authors.forename: David Y H
authors.initials: DY
authors.lastname: Choong
authors.forename: Diana M
authors.initials: DM
authors.lastname: Eccles
authors.forename: Gillian
authors.initials: G
authors.lastname: Mitchell
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
mesh_terms: D000328:Adult; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D019683:Penetrance; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C554482:KLLN protein, human; D025521:Tumor Suppressor Proteins