Novel t(5;11)(q32;q13.4) with NUMA1-PDGFRB fusion in a myeloid neoplasm with eosinophilia with response to imatinib mesylate

Cancer Genet. 2017 Apr:212-213:38-44. doi: 10.1016/j.cancergen.2017.03.004. Epub 2017 Mar 27.

Abstract

We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified by metaphase chromosome analysis, and rearrangement of the platelet-derived growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13.4 to a 150 kb genomic region containing three genes, including NUMA1. Mate pair sequencing analysis demonstrated NUMA1-PDGFRB fusion. The fusion protein includes coiled-coil domains of nuclear mitotic apparatus protein 1 (NuMA1, involved in protein homodimerization and heteroassociation) and tyrosine kinase domains of PDGFRB. Diverse rearrangements involving the PDGFRB gene have been identified in myeloid and lymphoid neoplasms with eosinophilia, but rearrangement of the nuclear mitotic apparatus protein 1 (NUMA1) gene has previously been reported in a human malignancy in only one instance, a NUMA1-RARA fusion caused by a t(11;17) translocation in a patient with acute promyelocytic leukemia. The NUMA1-PDGFRB fusion is the second instance of rearrangement of NUMA1, encoding an element of the mitotic apparatus, in human cancer.

Keywords: NUMA1; PDGFRB; t(5;11)(q32;q13.4).

Publication types

  • Case Reports

MeSH terms

  • Antigens, Nuclear / genetics*
  • Cell Cycle Proteins
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 5 / genetics
  • Eosinophilia / drug therapy*
  • Eosinophilia / genetics
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / genetics
  • Nuclear Matrix-Associated Proteins / genetics*
  • Oncogene Proteins, Fusion / genetics
  • Receptor, Platelet-Derived Growth Factor beta / genetics*
  • Translocation, Genetic
  • Treatment Outcome

Substances

  • Antigens, Nuclear
  • Cell Cycle Proteins
  • NUMA1 protein, human
  • Nuclear Matrix-Associated Proteins
  • Oncogene Proteins, Fusion
  • Imatinib Mesylate
  • PDGFRB protein, human
  • Receptor, Platelet-Derived Growth Factor beta