title: Novel germline mutations in BRCA2 gene among breast and breast-ovarian cancer families from Poland.
abstract: Identification of mutations in the BRCA2 gene and estimation of their clinical consequences for women and men treated in the Maria Sklodowska-Curie Memorial Cancer Center Warsaw, Poland in the years 1998-2008. The probands (97 women and 8 men) had a family history of breast and ovarian cancer (median age 46). The presence of molecular changes was examined in DNA isolated from peripheral blood lymphocytes. Germline mutations in 27 exons of the BRCA2 gene were screened by 'touchdown' PCR amplification, DHPLC and sequencing. Missense mutations were classified by multiple-sequences alignments of orthologous BRCA2 protein sequences with T-Coffee software. 39 molecular changes (8 novel) were identified in the BRCA2 gene in 105 investigated patients. In 12 patients the following pathogenic mutations were identified: 5467insT, 6174delT, 6192delAT, 6675delTA, 8141del5, 9152delT, 9326insA, 9631delC, IVS23-2A > G and E394X. The presence of 10 missense type mutations was detected including the following: D1420O, T1915 M, N3124I. The determination of pathogenic status of molecular variants detected in BRCA2 gene, described in the BIC mutation database as 'UV' depends on many parameters. Important is the assessment of the evolutionary conservation of their protein sequences and studying of the frequency of molecular variants detected in breast cancer patients and in population. A high diversity was found of the pathogenic mutations detected in BRCA2 gene in the Polish population.
authors.affiliation: Endocrinology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, WK Roentgen 5, 02-781, Warsaw, Poland. abalabas@coi.waw.pl
authors.forename: Aneta
authors.initials: A
authors.lastname: Balabas
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Skasko
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
authors.forename: Anna
authors.initials: A
authors.lastname: Niwinska
authors.forename: Pawel
authors.initials: P
authors.lastname: Blecharz
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D005190:Family; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D011044:Poland; D016133:Polymerase Chain Reaction
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