title: Germline alterations in the 53BP1 gene in breast and ovarian cancer families.
abstract: The conserved TP53-binding protein 1 (53BP1) is a central mediator of the DNA damage checkpoint and appears to be one of the sensors of DNA double-strand breaks (DSBs). Improper processing of DSBs can result in loss or rearrangement of genetic information, leading to cell death or tumorigenesis. 53BP1 interacts with both TP53 and ATM, key proteins involved in the monitoring of genomic integrity and regulation of apoptosis. 53BP1 is also required for the formation of BRCA1 foci and the C-terminal part of these two proteins display significant homology. Based on its biological function, the 53BP1 gene is a good candidate for being involved in cancer susceptibility. Consequently, in the current study patients belonging to 126 breast and/or ovarian cancer families were screened for germline mutations in the entire coding region of the 53BP1 gene. A number of sequence variants were found, but none of them appeared to associate with cancer predisposition. To our knowledge this is the first comprehensive screening of 53BP1 mutations in familial breast and ovarian cancer cases.
authors.affiliation: Department of Clinical Genetics, Oulu University Hospital/University of Oulu, P.O. Box 24, FIN-90029 OYS, Oulu, Finland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Rapakko
authors.forename: Katri
authors.initials: K
authors.lastname: Heikkinen
authors.forename: Sanna-Maria
authors.initials: SM
authors.lastname: Karppinen
authors.forename: Hannele
authors.initials: H
authors.lastname: Erkko
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1