title: Mutations in SETBP1 are recurrent in myelodysplastic syndromes and often coexist with cytogenetic markers associated with disease progression.
abstract: Whole exome sequencing was performed in a patient with myelodysplastic syndrome before and after progression to acute myeloid leukaemia. Mutations in several genes, including SETBP1, were identified following leukaemic transformation. Screening of 328 patients with myeloid disorders revealed SETBP1 mutations in 14 patients (4·3%), 7 of whom had -7/del(7q) and 3 had i(17)(q10), cytogenetic markers associated with shortened overall survival and increased risk of leukaemic evolution. SETBP1 mutations were frequently acquired at the time of leukaemic evolution, coinciding with increase of leukaemic blasts. These data suggest that SETBP1 mutations may play a role in MDS and chronic myelomonocytic leukaemia disease progression.
authors.affiliation: LLR Molecular Haematology Unit, NDCLS, RDM, John Radcliffe Hospital, Oxford, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernandez-Mercado
authors.forename: Andrea
authors.initials: A
authors.lastname: Pellagatti
authors.forename: Cristina
authors.initials: C
authors.lastname: Di Genua
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Larrayoz
authors.forename: Nils
authors.initials: N
authors.lastname: Winkelmann
authors.forename: Paula
authors.initials: P
authors.lastname: Aranaz
authors.forename: Adam
authors.initials: A
authors.lastname: Burns
authors.forename: Anna
authors.initials: A
authors.lastname: Schuh
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Boultwood
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D018450:Disease Progression; D059472:Exome; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics; D008297:Male; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D009687:Nuclear Proteins; C425066:SETBP1 protein, human
keywords: SETBP1; disease progression; mutation; myelodysplastic syndromes; whole exome sequencing