title: BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland.
abstract: Sixty-four Polish families with a history of breast and/or ovarian cancer were screened for mutations in the BRCA1/2 genes using a combination of denaturing high performance liquid chromatography (DHPLC) and sequencing. Two thirds (43/64; 67%) of the families were found to carry deleterious mutations, of which the most frequent were BRCA1 5382insC (n=22/43; 51%) and Cys61Gly (n=9/43; 20%). Two other recurrent mutations were BRCA1 185delAG (n=3) and 3819del5 (n=4), together accounting for 16% of the 43 mutation-positive cases. We also found three novel mutations (BRCA1 2991del5, BRCA2 6238ins2del21 and 8876delC) which combined with findings from our earlier study of 60 Northern Polish families. Moreover, screening of 43 BRCA1/2 negative families for the presence of large rearrangements by multiplex ligation-dependent probe amplification (MLPA) resulted in the finding of two additional BRCA1 mutations: a deletion of exons 1A, 1B and 2, and a deletion of exons 17-19, both present in single families. We conclude that the Polish population has a diverse mutation spectrum influenced by strong founder effects. However, families with strong breast/ovarian cancer history who are negative for these common mutations should be offered a complete BRCA gene screening, including MLPA analysis.
authors: Department of Biology and Genetics, Medical University of Gdansk, 80-210 Gdansk, Debinki 1, 80-210, Poland.
authors: Magdalena
authors: M
authors: Ratajska
authors: Izabela
authors: I
authors: Brozek
authors: Elzbieta
authors: E
authors: Senkus-Konefka
authors: Jacek
authors: J
authors: Jassem
authors: Magdalena
authors: M
authors: Stepnowska
authors: Grazia
authors: G
authors: Palomba
authors: Marina
authors: M
authors: Pisano
authors: Milena
authors: M
authors: Casula
authors: Giuseppe
authors: G
authors: Palmieri
authors: Ake
authors: A
authors: Borg
authors: Janusz
authors: J
authors: Limon
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D018703:Founder Effect; D015321:Gene Rearrangement; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction