title: A ZMYM2-FGFR1 8p11 myeloproliferative neoplasm with a novel nonsense RUNX1 mutation and tumor lysis upon imatinib treatment.
abstract: The 8p11 myeloproliferative neoplasm (8p11 MPN) is a rare disorder that is molecularly characterized by fusions of diverse partners to the tyrosine kinase receptor gene FGFR1. It can rapidly transform to acute myeloid leukemia. Here we report on a case with a t(8;13)(p11.2;q12.1) ZMYM2-FGFR1 fusion, with massive tumor lysis upon tyrosine kinase inhibition with imatinib. Upon reevaluation, we detected trisomy 21 in addition to the translocation. Sequencing revealed a nonsense c.958C →T RUNX1 mutation both at diagnosis and disease progression, resulting in a p.Arg320X carboxyl-terminal truncated RUNX1 protein. This is the first report on an 8p11 MPN with a trisomy 21 RUNX1 mutation.
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. a.buijs@umcutrecht.nl
authors.forename: Arjan
authors.initials: A
authors.lastname: Buijs
authors.forename: Merel
authors.initials: M
authors.lastname: van Wijnen
authors.forename: Dorine
authors.initials: D
authors.lastname: van den Blink
authors.forename: Mariëlle
authors.initials: M
authors.lastname: van Gijn
authors.forename: Saskia K
authors.initials: SK
authors.lastname: Klein
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001483:Base Sequence; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D002898:Chromosomes, Human, Pair 8; D018389:Codon, Nonsense; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000235:genetics*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D015275:Tumor Lysis Syndrome / Q000209:etiology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D018389:Codon, Nonsense; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D004268:DNA-Binding Proteins; D010879:Piperazines; D011743:Pyrimidines; C493728:RUNX1 protein, human; D014157:Transcription Factors; C111777:ZMYM2 protein, human; D000068877:Imatinib Mesylate; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1