title: Mutations predisposing to breast cancer in 12 candidate genes in breast cancer patients from Poland.
abstract: A number of genes other than BRCA1 and BRCA2 have been associated with breast cancer predisposition, and extended genetic testing panels have been proposed. It is of interest to establish the full spectrum of deleterious mutations in women with familial breast cancer.We performed whole-exome sequencing of 144 women with familial breast cancer and negative for 11 Polish founder mutations in BRCA1, CHEK2 and NBS1, and we evaluated the sequences of 12 known breast cancer susceptibility genes. A truncating mutation in a breast cancer gene was detected in 24 of 144 women (17%) with familial breast cancer. A BRCA2 mutation was detected in 12 cases, a (non-founder) BRCA1 mutation was detected in 5 cases, a PALB2 mutation was detected in 4 cases and an ATM mutation was detected in 2 cases. Polish women with familial breast cancer who are negative for founder mutations in BRCA1, CHEK2 and NBS1 should be fully screened for mutations in BRCA1, BRCA2 and PALB2. The PALB2 founder mutation c.509_519delGA should be included in the panel of Polish founder mutations.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: C
authors.initials: C
authors.lastname: Cybulski
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Lubiński
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Wokołorczyk
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Kuźniak
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Kashyap
authors.affiliation: Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Sopik
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Huzarski
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Gronwald
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Byrski
authors.affiliation: Tadeusz Koszarowski Regional Oncology Center, Opole, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Szwiec
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Jakubowska
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Górski
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Dębniak
authors.affiliation: Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.affiliation: Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: M R
authors.initials: MR
authors.lastname: Akbari
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D064447:Checkpoint Kinase 2 / Q000235:genetics; D004252:DNA Mutational Analysis; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D011044:Poland; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human
keywords: ATM; BRCA1; BRCA2; BRIP; CHEK2; PALB2; breast cancer; hereditary; mutation; whole-exome sequencing