title: Mutation profile of JAK2 transcripts in patients with chronic myeloproliferative neoplasias.
abstract: Here, we describe the JAK2 mutation profile in a series of approximately 20,000 blood samples from patients with clinically suspected myeloproliferative neoplasias. Using a sensitive reverse transcription-PCR and direct sequencing approach on RNA rather than DNA, we detected JAK2 mutations in exons 12-15 in approximately 20% of these patients. We identified new mutations in addition to the known V617F and exon 12 mutations, which were the most common. Most of the novel mutations are located in the pseudokinase domain and therefore are expected to relieve the autoinhibitory function of this domain on JAK2 kinase activity. Our data suggest that molecular testing of JAK2 mutations should not be restricted to the V617F and exon 12 mutations, but perhaps should extend to most of the pseudokinase domain coding region as well. Furthermore, mutation screening using RNA is highly sensitive and could replace DNA-based testing because of the relative abundance of target transcripts and the ease in detecting deletion of the entire exon.
authors.affiliation: Hematopathology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California.
authors.forename: Wanlong
authors.initials: W
authors.lastname: Ma
authors.affiliation: Leukemia and Bioimmunotherapy Department, M.D. Anderson Cancer Center, University of Texas, Houston, Texas.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Hematopathology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Hematopathology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California.
authors.forename: Chen-Hsiung
authors.initials: CH
authors.lastname: Yeh
authors.affiliation: Hematopathology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California.
authors.forename: Zhong J
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: Leukemia and Bioimmunotherapy Department, M.D. Anderson Cancer Center, University of Texas, Houston, Texas.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Hematopathology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California. Electronic address: maher.x.albitar@questdiagnostics.com.
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
mesh_terms: D002908:Chronic Disease; D004252:DNA Mutational Analysis; D055088:Early Detection of Cancer; D005091:Exons; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D009369:Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012334:RNA, Neoplasm; D053614:Janus Kinase 2