title: Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders.
abstract: The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases. Here we have investigated samples from 679 patients and controls for the nonreceptor tyrosine kinase JAK2 V617F mutation. Of the 480 myeloproliferative disorder (MPD) samples, the proportion of positive cases per disease subtype was 30 (20%) of 152 for atypical or unclassified MPD, 2 of 134 (2%) for idiopathic hypereosinophilic syndrome, 58 of 72 (81%) for polycythemia vera, 24 of 59 (41%) essential thrombocythemia (ET), and 15 of 35 (43%) for idiopathic myelofibrosis. V617F was not identified in patients with systemic mastocytosis (n = 28), chronic or acute myeloid leukemia (n = 35), secondary erythrocytosis (n = 4), or healthy controls (n = 160). Homozygosity for V617F was seen in 43% of mutant samples and was closely correlated with chromosome 9p uniparental disomy. Homozygosity was significantly less common in ET compared with other MPD subtypes. In 53 cases analyzed, the median level of PRV1 expression was significantly higher in V617F-positive cases compared with cases without the mutation. We conclude that V617F is widespread in MPDs. Detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, United Kingdom.
authors.forename: Amy V
authors.initials: AV
authors.lastname: Jones
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kreil
authors.forename: Katerina
authors.initials: K
authors.lastname: Zoi
authors.forename: Katherine
authors.initials: K
authors.lastname: Waghorn
authors.forename: Claire
authors.initials: C
authors.lastname: Curtis
authors.forename: Lingyan
authors.initials: L
authors.lastname: Zhang
authors.forename: Joannah
authors.initials: J
authors.lastname: Score
authors.forename: Rachel
authors.initials: R
authors.lastname: Seear
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Chase
authors.forename: Francis H
authors.initials: FH
authors.lastname: Grand
authors.forename: Helen
authors.initials: H
authors.lastname: White
authors.forename: Christine
authors.initials: C
authors.lastname: Zoi
authors.forename: Dimitris
authors.initials: D
authors.lastname: Loukopoulos
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Elisavet-Christine
authors.initials: EC
authors.lastname: Vervessou
authors.forename: Beate
authors.initials: B
authors.lastname: Schultheis
authors.forename: Michael
authors.initials: M
authors.lastname: Emig
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.forename: Eva
authors.initials: E
authors.lastname: Lengfelder
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2; D008297:Male; D018895:Microsatellite Repeats; D017720:Molecular Epidemiology; D020125:Mutation, Missense; D009196:Myeloproliferative Disorders / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2