title: Double heterozygotes among breast cancer patients analyzed for BRCA1, CHEK2, ATM, NBN/NBS1, and BLM germ-line mutations.
abstract: 17 double heterozygous (DH) breast cancer (BC) patients were identified upon the analysis of 5,391 affected women for recurrent Slavic mutations in BRCA1, CHEK2, NBN/NBS1, ATM, and BLM genes. Double heterozygosity was found for BRCA1 and BLM (4 patients), BRCA1 and CHEK2 (4 patients), CHEK2 and NBS1 (3 patients), BRCA1 and ATM (2 patients), CHEK2 and BLM (2 patients), CHEK2 and ATM (1 patient), and NBS1 and BLM (1 patient). DH BC patients were on average not younger than single mutation carriers and did not have an excess of bilateral BC; an additional non-breast tumor was documented in two BRCA1/BLM DH patients (ovarian cancer and lymphoplasmacytic lymphoma). Loss-of-heterozygosity (LOH) analysis of involved genes was performed in 5 tumors, and revealed a single instance of somatic loss of the wild-type allele (LOH at CHEK2 locus in BRCA1/CHEK2 double heterozygote). Distribution of mutations in patients and controls favors the hypothesis on multiplicative interaction between at least some of the analyzed genes. Other studies on double heterozygosity for BC-predisposing germ-line mutations are reviewed.
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, 197758, St.-Petersburg, Russia.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Sokolenko
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kluzniak
authors.forename: Elena V
authors.initials: EV
authors.lastname: Preobrazhenskaya
authors.forename: Ekatherina S
authors.initials: ES
authors.lastname: Kuligina
authors.forename: Aglaya G
authors.initials: AG
authors.lastname: Iyevleva
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Aleksakhina
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Mitiushkina
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Gorodnova
authors.forename: Alexandr A
authors.initials: AA
authors.lastname: Bessonov
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Togo
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011044:Poland; D053484:RecQ Helicases / Q000235:genetics*; D002094:Republic of Belarus; D012426:Russia
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; C097151:Bloom syndrome protein; D053484:RecQ Helicases