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FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome

Nature Genetics volume 18, pages 84–87 (1998)Cite this article

Abstract

Various histological subtypes of leukaemia and lymphoma are associated with diagnostic chromosome translations1–4, and substantial strides have been made in determining the specific oncogenes targetted by those translocations. We report the cloning of a novel fusion oncogene associated with a unique leukaemia/lymphoma syndrome. Patients afflicted with this syndrome present with lymphoblastic lymphoma and a myelopro I iterative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow, which generally progress to full-blown acute myelogenous leukaemia within a year of diagnosis5–9. A specific chromosome translocation, t(8;13)(p11;q11–12), is found in both lymphoma and myeloid leukaemia cells from these patients, supporting bi-lineage differentiation from a transformed stem cell6–8. We find that the 8p11 translocation breakpoints, in each of four patients, interrupt intron 8 of the fibroblast growth factor receptor 1 gene (FGFR1). These translocations are associated with aberrant transcripts in which four predicted zinc-finger domains, contributed by a novel and widely expressed chromosome-13 gene (ZNF198), are fused to the FGFR1 tyrosine-kinase domain. Transient expression studies show that the ZNF198–FGFR1 fusion transcript directs the synthesis of an approximately 87-kD polypeptide, localizing predominantly to the cytoplasm. Our studies demonstrate an FGFR1 oncogenic role and suggest a tumorigenic mechanism in which ZNF198–FGFR1 activation results from ZNF198 zinc-finger-mediated homodimerization.

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Authors and Affiliations

  1. Department of Pathology, Brigham and Women′s Hospital, 75 Francis Street, Boston, Massachusetts, 02115, USA

    Sheng Xiao, Jon C. Aster & Jonathan A. Fletcher

  2. Yale University School of Medicine, 336 BCCM, 295 Congress Avenue, New Haven, Connecticut, 06536-0812, USA

    Srinivasa R. Nalabolu & Sherman M. Weissman

  3. Centerfor Genome Research, Whitehead Institute/MIT, 9 Cambridge Center, Cambridge, Massachusetts, 02142, USA

    Junli Ma & Thomas J. Hudson

  4. Department of Pathology, University of Maryland Medical Center, 22 South Greene Street, Baltimore, Maryland, 21201-1595, USA

    Lynne Abruzzo

  5. Hematopathology Section, National Cancer Institute, Building 10, Room 2N202, 9000 Rockville Pike, Bethesda, Maryland, 20892-1500, USA

    Elaine S. Jaffe

  6. Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, 02115, USA

    Richard Stone & Jonathan A. Fletcher

  7. Division of Hematology-Oncology, Children′s Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Jonathan A. Fletcher

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Xiao, S., Nalabolu, S., Aster, J. et al. FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Nat Genet 18, 84–87 (1998). https://doi.org/10.1038/ng0198-84

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