title: Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland.
abstract: Germline mutations in the BRCA1 and BRCA2 genes account for the majority of high-risk breast/ovarian cancer families, depending on the population studied. Previously, BRCA1 mutations were described in women from Western Poland. To further characterize the spectrum of BRCA1 mutations and the impact of BRCA2 mutations in Poland, we have analyzed 25 high-risk breast and/or ovarian cancer families from North-Eastern Poland for mutations in all coding exons of the BRCA1 and BRCA2 genes, using combined heteroduplex analysis/SSCP followed by direct DNA sequence analysis. Out of 25 probands a total of five (20%) carried three recurrent BRCA1 mutations (300T>G, 3819del5, 5382insC). The 300T>G mutation accounted for 60% (3/5) of BRCA1 mutations and allelotyping suggested a common founder of this mutation. No unique mutations were found. In addition, we identified three BRCA2 (12%) mutations, one recurrent 4075delGT, and two novel frameshift mutations, 7327ins/dupl19 and 9068delA. We conclude that 30% of high-risk families from North-Eastern Poland may be due to recurrent BRCA1 and unique BRCA2 mutations. Intriguingly, the BRCA1 mutation spectrum seems to be different within subregions of Poland.
authors.affiliation: National Institute of Oncology, Department of Molecular Biology, Budapest, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: van Der Looij
authors.forename: B
authors.initials: B
authors.lastname: Wysocka
authors.forename: I
authors.initials: I
authors.lastname: Brozek
authors.forename: J
authors.initials: J
authors.lastname: Jassem
authors.forename: J
authors.initials: J
authors.lastname: Limon
authors.forename: E
authors.initials: E
authors.lastname: Olah
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005819:Genetic Markers / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D011044:Poland; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors