title: A Polycythemia Vera JAK2 Mutation Masquerading as a Duodenal Cancer Mutation.
abstract: Next-generation sequencing (NGS) is increasingly being used in cancer care to identify both somatic tumor driver mutations that can be targeted for therapy, and heritable mutations in the germline associated with increased cancer risk. This report presents a case of a JAK2 V617F mutation falsely identified as a duodenal cancer mutation via NGS. The patient was found to have a history of polycythemia vera, a disorder with a high incidence of JAK2 somatic mutations. Buccal cell DNA showed heterozygosity for the mutation, suggesting that it was potentially germline. However, subsequent resequencing of tumor, adjacent normal tissue, and fingernail DNA confirmed the mutation was somatic, and its presence in tumor and buccal cells resulted from contaminating blood cells. This report highlights important nuances of NGS that can lead to misinterpretation of results with potential clinical implications.
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Justin
authors.initials: J
authors.lastname: Lee
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Axilbund
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: W Brian
authors.initials: WB
authors.lastname: Dalton
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Laheru
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Stanley
authors.initials: S
authors.lastname: Watkins
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Chu
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Karen
authors.initials: K
authors.lastname: Cravero
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Berry
authors.initials: B
authors.lastname: Button
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Kelly
authors.initials: K
authors.lastname: Kyker-Snowman
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Ian
authors.initials: I
authors.lastname: Waters
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Gocke
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Josh
authors.initials: J
authors.lastname: Lauring
authors.affiliation: From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.|From The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, and The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Ben Ho
authors.initials: BH
authors.lastname: Park
mesh_terms: D015746:Abdominal Pain / Q000209:etiology; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001773:Blood Cells; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D059018:DNA Contamination; D003937:Diagnosis, Differential; D004379:Duodenal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004386:Duodenum / Q000000981:diagnostic imaging; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D017051:Hospice Care; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D002955:Leucovorin / Q000627:therapeutic use; D009061:Mouth Mucosa / Q000166:cytology; D009154:Mutation; D009262:Nails; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D016577:Pancreaticoduodenectomy / Q000379:methods; D018962:Phlebotomy; D011087:Polycythemia Vera / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D017422:Sequence Analysis, DNA; D014057:Tomography, X-Ray Computed
chemical_list: D009944:Organoplatinum Compounds; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin