title: Comprehensive BRCA1 and BRCA2 mutational profile in Lithuania.
abstract: There is limited knowledge about the BRCA1/2 mutational profile in Lithuania. We aimed to define the full BRCA1 and BRCA2 mutational spectrum and the clinically relevant prevalence of these gene mutations in Lithuania. A data set of 753 unrelated probands, recruited through a clinical setting, was used and consisted of 380 female breast cancer cases, 213 epithelial ovarian cancer cases, 20 breast and ovarian cancer cases, and 140 probands with positive family history of breast or ovarian cancer. A comprehensive mutation analysis of the BRCA1/2 genes by high resolution melting analysis coupled with Sanger sequencing and multiplex ligation-dependent probe amplification analysis was performed. Genetic analysis revealed 32 different pathogenic germline BRCA1/2 mutations: 20 in the BRCA1 gene and 12 in the BRCA2 gene, including four different large genomic rearrangements in the BRCA1 gene. In all, 10 novel BRCA1/2 mutations were found. Nine different recurrent BRCA1 mutations and two recurrent BRCA2 mutations were identified, which comprised 90.4% of all BRCA1/2 mutations. BRCA1 exon 1-3 deletion and BRCA2 c.658_659del are reported for the first time as recurrent mutations, pointing to a possible Baltic founder effect. Approximately 7% of breast cancer and 22% of ovarian cancer patients without family history and an estimated 0.5-0.6% of all Lithuanian women were found to be carriers of mutations in the BRCA1 or BRCA2 gene.
authors: Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; State Research Institute, Innovative Medicine Center, Vilnius, Lithuania. Electronic address: ramunas.janavicius@santa.lt.
authors: Ramūnas
authors: R
authors: Janavičius
authors: Clinics of Internal, Family Medicine and Oncology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania; Department of Gynecology, Centre of Women's Physiology and Pathology, Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania.
authors: Vilius
authors: V
authors: Rudaitis
authors: National Center of Pathology, Vilnius, Lithuania.
authors: Ugnius
authors: U
authors: Mickys
authors: State Research Institute, Innovative Medicine Center, Vilnius, Lithuania; Public Institution Centro Poliklinika, Vilnius, Lithuania.
authors: Pavel
authors: P
authors: Elsakov
authors: Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; Clinics of Internal, Family Medicine and Oncology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
authors: Laimonas
authors: L
authors: Griškevičius
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008097:Lithuania; D009154:Mutation; D059645:Mutation Rate; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C551750:BRCA2 protein, human; C508053:ERBB2 protein, human
keywords: BRCA1; BRCA2; genetic testing; hereditary breast and ovarian cancer; oncogenetics