title: Evidence for a pathogenic role of BRCA1 L1705P and W1837X germ-line mutations.
abstract: BRCA1 L1705P (c.5114T>C) has been classified in the NCBI SNP database as the variant with uncertain significance and is absent in major BRCA1 databases. BRCA1 W1837X (c.5511G>A) results in a loss of only last 27 residues of BRCA1 protein, thus its pathogenic role still requires a confirmation. This report describes two breast cancer (BC) patients carrying BRCA1 L1705P and W1837X germ-line mutations, respectively. Significant evidence for BC-predisposing impact of the mentioned mutations have been obtained: (1) both index cases presented with the triple-negative receptor status of BC disease; (2) complete segregation with BRCA1-related cancers was observed in the families of these patients; (3) somatic loss of the remaining (wild-type) BRCA1 allele was detected in tumor tissues of the affected women. The results of this study have to be taken into account while providing genetic counseling to cancer patients and while considering the use of BRCA1-specific therapeutic compounds for BC treatment.
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, Russia, 197758.|St.-Petersburg Pediatric Medical University, St. Petersburg, Russia, 194100.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Sokolenko
authors.affiliation: City Cancer Center, St. Petersburg, Russia, 197758.
authors.forename: Nikita M
authors.initials: NM
authors.lastname: Volkov
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, Russia, 197758.|St.-Petersburg Pediatric Medical University, St. Petersburg, Russia, 194100.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Preobrazhenskaya
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, Russia, 197758.|St.-Petersburg Pediatric Medical University, St. Petersburg, Russia, 194100.
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Suspitsin
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, Russia, 197758.
authors.forename: Aigul R
authors.initials: AR
authors.lastname: Garifullina
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, Russia, 197758.|St.-Petersburg Pediatric Medical University, St. Petersburg, Russia, 194100.
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Ivantsov
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, Russia, 197758.|St.-Petersburg Pediatric Medical University, St. Petersburg, Russia, 194100.
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Togo
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, Russia, 197758. evgeny@imyanitov.spb.ru.|St.-Petersburg Pediatric Medical University, St. Petersburg, Russia, 194100. evgeny@imyanitov.spb.ru.|I.I. Mechnikov North-Western Medical University, St. Petersburg, Russia, 191015. evgeny@imyanitov.spb.ru.|St.-Petersburg State University, St. Petersburg, Russia, 199034. evgeny@imyanitov.spb.ru.
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm; D005260:Female; D019398:Genes, BRCA1; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D010375:Pedigree
chemical_list: D004273:DNA, Neoplasm
keywords: BRCA1; Breast cancer; Hereditary predisposition; Mutation; PARP inhibitors