Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia-associated myeloproliferative neoplasms

Nicole Naumann; Juliana Schwaab; Georgia Metzgeroth; Mohamad Jawhar; Claudia Haferlach; Gudrun Göhring; Brigitte Schlegelberger; Christian T Dietz; Susanne Schnittger; Sina Lotfi; Michael Gärtner; Tu-Anh Dang; Wolf-Karsten Hofmann; Nicholas C P Cross; Andreas Reiter; Alice Fabarius

doi:10.1002/gcc.22287

Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia-associated myeloproliferative neoplasms

Genes Chromosomes Cancer. 2015 Dec;54(12):762-70. doi: 10.1002/gcc.22287. Epub 2015 Sep 10.

Authors

Nicole Naumann¹, Juliana Schwaab¹, Georgia Metzgeroth¹, Mohamad Jawhar¹, Claudia Haferlach², Gudrun Göhring³, Brigitte Schlegelberger³, Christian T Dietz¹, Susanne Schnittger², Sina Lotfi⁴, Michael Gärtner⁵, Tu-Anh Dang⁶, Wolf-Karsten Hofmann¹, Nicholas C P Cross^{7

8}, Andreas Reiter¹, Alice Fabarius¹

Affiliations

¹ III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
² MLL Münchner Leukämielabor GmbH, München, Germany.
³ Institut Für Humangenetik, Medizinische Hochschule Hannover, Hannover, Germany.
⁴ Onkologie MVZ Am Siloah St. Trudpert Klinikum Pforzheim, Pforzheim, Germany.
⁵ Onkologisches Ambulanzzentrum Hannover, Hannover, Germany.
⁶ Medizinische Klinik V, Klinikum Darmstadt, Darmstadt, Germany.
⁷ Wessex Regional Genetics Laboratory, Salisbury, UK.
⁸ Faculty of Medicine, University of Southampton, UK.

PMID: 26355392
DOI: 10.1002/gcc.22287

Abstract

In eosinophilia-associated myeloproliferative neoplasms (MPN-eo), constitutive activation of protein tyrosine kinases (TK) as consequence of translocations, inversions, or insertions and creation of TK fusion genes is recurrently observed. The most commonly involved TK and their potential TK inhibitors include PDGFRA at 4q12 or PDGFRB at 5q33 (imatinib), FGFR1 at 8p11 (ponatinib), and JAK2 at 9p24 (ruxolitinib). We here report the identification of three new PDGFRB fusion genes in three male MPN-eo patients: MPRIP-PDGFRB in a case with t(5;17)(q33;p11), CPSF6-PDGFRB in a case with t(5;12)(q33;q15), and GOLGB1-PDGFRB in a case with t(3;5)(q13;q33). The fusion proteins identified by 5'-rapid amplification of cDNA ends polymerase chain reaction (PCR) or DNA-based long distance inverse PCR are predicted to contain the TK domain of PDGFRB. The partner genes contain domains like coiled-coil structures, which are likely to cause dimerization and activation of the TK. In all patients, imatinib induced rapid and durable complete remissions.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Aged
Aged, 80 and over
Antineoplastic Agents / therapeutic use
Chromosomes, Human, Pair 12 / genetics
Chromosomes, Human, Pair 17 / genetics
Chromosomes, Human, Pair 3 / genetics
Chromosomes, Human, Pair 5 / genetics
Cytogenetic Analysis
Eosinophilia / drug therapy
Eosinophilia / genetics*
Eosinophilia / pathology
Gene Fusion*
Golgi Matrix Proteins
Humans
Imatinib Mesylate / therapeutic use
In Situ Hybridization, Fluorescence
Male
Membrane Proteins / genetics*
Middle Aged
Myeloproliferative Disorders / drug therapy
Myeloproliferative Disorders / genetics*
Myeloproliferative Disorders / pathology
Polymerase Chain Reaction
Receptor, Platelet-Derived Growth Factor beta / genetics*
Remission Induction
Translocation, Genetic*
mRNA Cleavage and Polyadenylation Factors / genetics*

Substances

Adaptor Proteins, Signal Transducing
Antineoplastic Agents
Golgi Matrix Proteins
MPRIP protein, human
Membrane Proteins
cleavage factor Im, human
mRNA Cleavage and Polyadenylation Factors
macrogolgin
Imatinib Mesylate
PDGFRB protein, human
Receptor, Platelet-Derived Growth Factor beta

Supplementary concepts

Myeloproliferative Disorder, Chronic, with Eosinophilia