title: Mutational analysis of BRCA1/2 in a group of 134 consecutive ovarian cancer patients. Novel and recurrent BRCA1/2 alterations detected by next generation sequencing.
abstract: The importance of proper mutational analysis of BRCA1/2 in individuals at risk for hereditary breast and ovarian cancer syndrome is widely accepted. Standard genetic screening includes targeted analysis of recurrent, population-specific mutations. The purpose of the study was to establish the frequency of germline BRCA1/2 mutations in a group of 134 unrelated patients with primary ovarian cancer. Next generation sequencing analysis revealed a presence of 20 (14.9%) mutations, where 65% (n = 13) were recurrent BRCA1 alterations included in the standard diagnostic panel in northern Poland. However, the remaining seven BRCA1/2 mutations (35%) would be missed by the standard approach and were detected in unique patients. A substantial proportion (n = 5/12; 41%) of mutation-positive individuals with complete family history reported no incidence of breast or ovarian cancer in their relatives. This observation, together with the raising perspectives for personalized therapy targeting BRCA1/2 signaling pathways indicates the necessity of comprehensive genetic screening in all ovarian cancer patients. However, due to the limited sensitivity of the standard genetic screening presented in this study (65%) an application of next generation sequencing in molecular diagnostics of BRCA1/2 genes should be considered.
authors.affiliation: Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-210, Gdansk, Poland, mratajska@gumed.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ratajska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Krygier
authors.forename: Maciej
authors.initials: M
authors.lastname: Stukan
authors.forename: Alina
authors.initials: A
authors.lastname: Kuźniacka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Koczkowska
authors.forename: Mirosław
authors.initials: M
authors.lastname: Dudziak
authors.forename: Marcin
authors.initials: M
authors.lastname: Śniadecki
authors.forename: Jarosław
authors.initials: J
authors.lastname: Dębniak
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wydra
authors.forename: Izabela
authors.initials: I
authors.lastname: Brozek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Janusz
authors.initials: J
authors.lastname: Limon
authors.forename: Bartosz
authors.initials: B
authors.lastname: Wasąg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D011044:Poland