title: Fusion of PDGFRB to two distinct loci at 3p21 and a third at 12q13 in imatinib-responsive myeloproliferative neoplasms.
abstract: We identified four patients who presented with BCR-ABL1 negative myeloproliferative neoplasms and cytogenetically visible abnormalities of chromosome band 5q31-35. Fluorescence in situ hybridization indicated that the platelet-derived growth factor receptor beta gene (PDGFRB) was disrupted in all four cases and 5' rapid amplification of cDNA ends identified in-frame mRNA fusions between PDGFRB and WDR48 (3p21), GOLGA4 (3p21) and BIN2 (12q13). Strikingly, all three genes encode proteins involving intracellular trafficking. Imatinib, a known inhibitor of PDGFRbeta, selectively blocked the growth of t(3;5) myeloid colonies and produced clinically significant responses in all patients. We conclude that PDGFRB fuses to diverse partner genes in atypical myeloproliferative neoplasms (MPNs). Although very rare, identification of these fusions is critical for proper management of affected individuals.
authors.affiliation: University of Southampton, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Hidalgo-Curtis
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Allistair
authors.initials: A
authors.lastname: Stark
authors.forename: Anthony
authors.initials: A
authors.lastname: Stark
authors.forename: Michael
authors.initials: M
authors.lastname: Jeng
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.forename: Andrew
authors.initials: A
authors.lastname: Chase
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Francis H
authors.initials: FH
authors.lastname: Grand
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002648:Child; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta