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

• Published in: Breast cancer research and treatment 2012-07, Vol.134 (2), p.543-547
• Main Authors: Thompson, Ella R., Gorringe, Kylie L., Choong, David Y. H., Eccles, Diana M., Mitchell, Gillian, Campbell, Ian G.
• Format: Article
• Language: English
• Subjects: Adult; Analysis; Base Sequence; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Cancer; Cancer research; Case-Control Studies; Cohort Studies; DNA; DNA Mutational Analysis; Female; Gene Frequency; Gene mutations; Genes; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Genetic research; Germ-Line Mutation; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Loss of Heterozygosity; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Molecular Sequence Data; Mutation; Oncology; Penetrance; Preclinical Study; Sequence Deletion; Tumor proteins; Tumor Suppressor Proteins - genetics; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-012-2088-3

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.