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: Arjan Buijs, Merel van Wijnen, Dorine van den Blink, Mariëlle van Gijn, Saskia K Klein
• Journal: Cancer genetics (Cancer Genet) Vol. 206 Issue 4 Pg. 140-4 (Apr 2013) ISSN: 2210-7762 [Print] United States
• PMID: 23751892 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzamides
• Codon, Nonsense
• Core Binding Factor Alpha 2 Subunit
• DNA Primers
• DNA-Binding Proteins
• Piperazines
• Pyrimidines
• RUNX1 protein, human
• Transcription Factors
• ZMYM2 protein, human
• Imatinib Mesylate
• FGFR1 protein, human
• Receptor, Fibroblast Growth Factor, Type 1

Topics

• Antineoplastic Agents (adverse effects, therapeutic use)
• Base Sequence
• Benzamides (adverse effects, therapeutic use)
• Chromosomes, Human, Pair 8
• Codon, Nonsense
• Core Binding Factor Alpha 2 Subunit (genetics)
• DNA Primers
• DNA-Binding Proteins (genetics)
• Female
• Humans
• Imatinib Mesylate
• Karyotyping
• Middle Aged
• Myeloproliferative Disorders (drug therapy, genetics)
• Piperazines (adverse effects, therapeutic use)
• Pyrimidines (adverse effects, therapeutic use)
• Real-Time Polymerase Chain Reaction
• Receptor, Fibroblast Growth Factor, Type 1 (genetics)
• Transcription Factors (genetics)
• Tumor Lysis Syndrome (etiology)