title: Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families.
abstract: BACKGROUND
  BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and/or ovarian cancer families.
  
  
  METHODS
  Altogether 61 index patients of Northern Finnish breast and/or ovarian cancer families were analyzed by Multiplex ligation-dependent probe amplification (MLPA) method in order to identify exon deletions and duplications in BRCA1, BRCA2 and PALB2. The families have been comprehensively screened for germline mutation in these genes by conventional methods of mutation analysis and were found negative.
  
  
  RESULTS
  We identified one large deletion in BRCA1, deleting the most part of the gene (exon 1A-13) in one family with family history of ovarian cancer. No large genomic rearrangements were identified in either BRCA2 or PALB2.
  
  
  CONCLUSIONS
  In Finland, women eligible for BRCA1 or BRCA2 mutation screening, when found negative, could benefit from screening for large genomic rearrangements at least in BRCA1. On the contrary, the genomic rearrangements in PALB2 seem not to contribute to the hereditary breast cancer susceptibility.
authors.affiliation: Laboratory of Cancer Genetics, Oulu University Hospital and University of Oulu/Biocenter Oulu, Oulu, Finland. katri.pylkas@oulu.fi
authors.forename: Katri
authors.initials: K
authors.lastname: Pylkäs
authors.forename: Hannele
authors.initials: H
authors.lastname: Erkko
authors.forename: Jenni
authors.initials: J
authors.lastname: Nikkilä
authors.forename: Szilvia
authors.initials: S
authors.lastname: Sólyom
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
mesh_terms: D017668:Age of Onset; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins