title: Challenges in Interpreting Germline Mutations in BARD1 and ATM in Breast and Ovarian Cancer Patients.
abstract: Next-generation sequencing promotes identification of mutations in non-BRCA1/2 genes in hereditary cancer families. The contribution of mutations in moderate penetrance genes to hereditary cancer risk is not well established. Here, we report a family with early onset breast and fallopian tube cancer that was identified as carrying germline mutations in BARD1 and ATM genes. Loss of heterozygosity studies suggest a causative role of the BARD1 mutation in the development of primary peritoneal cancer, but fail to confirm an association between germline ATM mutations and breast cancer development in this family. Complexities in interpreting implications of mutations in moderate-risk cancer susceptibility genes are discussed.
authors.affiliation: Division of Hematology-Oncology, Beth-Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Kimberly
authors.initials: K
authors.lastname: DeLeonardis
authors.affiliation: Division of Hematology-Oncology, Beth-Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Kristin
authors.initials: K
authors.lastname: Sedgwick
authors.affiliation: Division of Hematology-Oncology, Beth-Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Olga
authors.initials: O
authors.lastname: Voznesensky
authors.affiliation: Cancer Genetic Counseling Program, Yale Cancer Center/Yale School of Medicine, New Haven, Connecticut.
authors.forename: Ellen
authors.initials: E
authors.lastname: Matloff
authors.affiliation: Division of Medical Oncology, Yale Cancer Center/Yale School of Medicine, New Haven, Connecticut.
authors.forename: Erin
authors.initials: E
authors.lastname: Hofstatter
authors.affiliation: Division of Hematology-Oncology, Beth-Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Steven
authors.initials: S
authors.lastname: Balk
authors.affiliation: Division of Hematology-Oncology, Beth-Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
mesh_terms: D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; BARD1; breast cancer; ovarian cancer; primary peritoneal cancer