title: PALB2 mutations in familial breast and pancreatic cancer.
abstract: PALB2 (Partner And Localizer of BRCA2) binds to and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1-2% of familial breast cancer and 3-4% of familial pancreatic cancer cases. The goal of this study was to evaluate the prevalence of PALB2 mutations in women with breast cancer without BRCA1/2 mutations who also had a personal or family history of pancreatic cancer. PALB2 mutation analysis was performed in 94 non-BRCA1/2 breast cancer patients with a personal or family history of pancreatic cancer. Two truncating PALB2 mutations, c.3549C>CA and c.2962C>CT, were identified resulting in a mutation prevalence of 2.1%. The proband found to carry the c.3549C>CA PALB2 mutation had a mother diagnosed with both breast and pancreatic cancer; this relative was subsequently confirmed to carry the identical mutation. The proband with the c.2962C>CT mutation had a father and paternal aunt diagnosed with pancreatic cancer; neither relative was available for testing. Two novel PALB2 missense variants were also found, one of which was deemed potentially deleterious. The prevalence rate of PALB2 mutations in a non-BRCA1/2 breast cancer population specifically selected for a family history of pancreatic cancer does not appear to be significantly increased compared to that observed in other breast cancer populations studied thus far. Further evaluation is needed to determine the prevalence of PALB2 mutations and the clinical utility of such testing in those individuals affected with both breast and pancreatic cancers.
authors.affiliation: Section of Medical Oncology, Yale Cancer Center, Yale School of Medicine, 333 Cedar Street, PO Box 208032, New Haven, CT 06520-8032, USA. erin.hofstatter@yale.edu
authors.forename: Erin W
authors.initials: EW
authors.lastname: Hofstatter
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
authors.forename: Judy
authors.initials: J
authors.lastname: Garber
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.forename: Kathryn
authors.initials: K
authors.lastname: Componeschi
authors.forename: Leigh
authors.initials: L
authors.lastname: Boghossian
authors.forename: Penelope L
authors.initials: PL
authors.lastname: Miron
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins