title: Germline BAP1 mutations misreported as somatic based on tumor-only testing.
abstract: We present three unrelated patients with germline mutations in BAP1 misreported as somatic mutations. All had strong family histories of cancer. One of these patients presented with an invasive breast cancer with the tumor tissue showing partial loss of the mutant rather than the wild type allele, suggesting that the germline BAP1 mutation didn't contribute to breast cancer development in this patient. This data highlights the importance of sequencing matching germline and tumor DNA for proper assessment of somatic versus germline mutation status. In patients with somatic mutations reported from laboratories carrying out tumor-only genomic testing, the possibility that a variant may be a germline mutation should be considered, especially if the personal and/or family history suggests hereditary cancer predisposition. Since tumor-only testing can reveal germline mutations, ethical issues for patients being tested should be considered including proper consent and genetic counseling.
authors.affiliation: Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH, USA. mohamed.abdel-rahman@osumc.edu.|Division of Human Genetics, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. mohamed.abdel-rahman@osumc.edu.|Department of Pathology, Menoufiya University, Shebin El-Kom, Egypt. mohamed.abdel-rahman@osumc.edu.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Abdel-Rahman
authors.affiliation: Division of Human Genetics, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Karan
authors.initials: K
authors.lastname: Rai
authors.affiliation: Division of Human Genetics, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Pilarski
authors.affiliation: Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH, USA.
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Davidorf
authors.affiliation: Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Cebulla
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*; D014604:Uveal Neoplasms / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; Familial cancer; Hereditary cancer predisposition; Uveal melanoma