title: Screening for large genomic rearrangements of the BRIP1 and CHK1 genes in Finnish breast cancer families.
abstract: In search for susceptibility genes that could explain an additional portion of familial breast cancer clustering in Finland, we set out to evaluate the presence of large genomic rearrangements in two candidate genes, BRIP1 and CHK1. BRIP1 is a BRCA1 associated protein that is mutated in a fraction of familial breast cancer and Fanconi anemia cases. To date, the role of large BRIP1 deletions in breast cancer susceptibility is not well-characterized. CHK1 is a critical maintainer of cell cycle checkpoints and genomic stability, and is also involved in the BRCA1 and FA protein signalling pathways. Although CHK1 is a very important protein for cell cycle and DNA integrity maintenance control, no mutations in this gene has yet been associated with predisposition to cancer. For the present study, blood DNA from affected index persons of 111 Northern Finnish breast cancer families was assessed for possible constitutional exonic deletions or amplifications in the BRIP1 and CHK1 genes by using the multiplex ligation-dependent probe amplification method. Our results showed that exonic deletions or amplifications affecting the BRIP1 and CHK1 genes seem not to contribute to hereditary breast cancer susceptibility in the Finnish population. To our knowledge, this is the first attempt to determine the existence of large CHK1 deletions in familial breast cancer or in any disease with a hereditary background.
authors.affiliation: Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, Oulu University Hospital, University of Oulu, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Solyom
authors.forename: Katri
authors.initials: K
authors.lastname: Pylkäs
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000071877:Checkpoint Kinase 1; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005190:Family; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D005387:Finland; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008403:Mass Screening; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011494:Protein Kinases / Q000235:genetics*; D020365:RNA Helicases / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000618935:BRIP1 protein, human; D020365:RNA Helicases