title: A new potential oncogenic mutation in the FERM domain of JAK2 in BCR/ABL1-negative and V617F-negative chronic myeloproliferative neoplasms revealed by a comprehensive screening of 17 tyrosine kinase coding genes.
abstract: BCR/ABL1-negative chronic myeloproliferative neoplasms (CMPNs) are a heterogeneous group of clonal hematological malignancies. Over recent years, some genetic events in tyrosine kinase (TK) genes have been described as causal events of these diseases. To identify new genetic aberrations underlying these diseases, we used denaturing high performance liquid chromatography and fluorescence in situ hybridization (FISH) to analyze 17 genes from two receptor-TK families (III and IV) and from three cytoplasmic-TK families (Syk, Abl, and Jak) on samples from 44 BCR/ABL1-negative and JAK2(V617F)-negative CMPN patients with different clinical phenotypes. Although screening by FISH did not reveal novel chromosomal aberrations, several sequence changes were detected. None of them were frequent events, but we identified a new potential activating mutation in the FERM domain of JAK2(R340Q). None of the germline JAK2(V617F) single-nucleotide polymorphisms detected differed in distribution between patients and control subjects. In summary, data presented here show that these genes are not frequently mutated or rearranged in CMPNs, suggesting that molecular events causing these disorders must be located in other genes.
authors.affiliation: Department of Genetics, University of Navarra, Pamplona, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Aranaz
authors.forename: Cristina
authors.initials: C
authors.lastname: Ormazábal
authors.forename: Cristina
authors.initials: C
authors.lastname: Hurtado
authors.forename: Ignacio
authors.initials: I
authors.lastname: Erquiaga
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Marina
authors.initials: M
authors.lastname: García-Delgado
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Novo
authors.forename: José L
authors.initials: JL
authors.lastname: Vizmanos
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D002908:Chronic Disease; D005091:Exons / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2 / Q000737:chemistry* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000201:enzymology* / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017434:Protein Structure, Tertiary
chemical_list: D016044:Fusion Proteins, bcr-abl; D053614:Janus Kinase 2