title: Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders.
abstract: The BCR-ABL-negative chronic myeloproliferative disorders (CMPD) and myelodysplastic/myeloproliferative diseases (MDS/MPD) are a spectrum of related conditions for which the molecular pathogenesis is poorly understood. Translocations that disrupt and constitutively activate the platelet-derived growth factor receptor beta(PDGFRB) gene at chromosome band 5q33 have been described in some patients, the most common being the t(5;12)(q33;p13). An accurate molecular diagnosis of PDGFRB-rearranged patients has become increasingly important since recent data have indicated that they respond very well to imatinib mesylate therapy. In this study, we have tested nine patients with a CMPD or MDS/MPD and a translocation involving 5q31-33 for disruption of PDGFRB by two-colour fluorescence in situ hybridization (FISH) using differentially labelled, closely flanking probes. Normal control interphase cells gave a false positive rate of 3% (signals more than one signal width apart). Six patients showed a pattern of one fused signal (from the normal allele) and one pair of signals separated by more than one signal width in > 85% of interphase cells, indicating that PDGFRB was disrupted. These individuals had a t(1;5)(q21;q33), t(1;5)(q22;q31), t(1;3;5)(p36;p21;q33), t(2;12;5)(q37;q22;q33), t(3;5) (p21;q31) and t(5;14)(q33;q24) respectively. The remaining three patients with a t(1;5)(q21;q31), t(2;5)(p21;q33) and t(5;6)(q33;q24-25) showed a normal pattern of hybridization, with > or = 97% interphase cells with two fusion signals. We conclude that two-colour FISH is useful to determine the presence of a PDGFRB rearrangement, although, as we have shown previously, this technique may not detect subtle complex translocations at this locus. Our data indicate that several PDGFRB partner genes remain to be characterized.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, UK.
authors.forename: E Joanna
authors.initials: EJ
authors.lastname: Baxter
authors.forename: Shashikant
authors.initials: S
authors.lastname: Kulkarni
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Vizmanos
authors.forename: Rina
authors.initials: R
authors.lastname: Jaju
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: George
authors.initials: G
authors.lastname: Hughes
authors.forename: Zoryana
authors.initials: Z
authors.lastname: Salamanchuk
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Pocock
authors.forename: Raymond
authors.initials: R
authors.lastname: Dang
authors.forename: Carrie
authors.initials: C
authors.lastname: Fidler
authors.forename: James S
authors.initials: JS
authors.lastname: Wainscoat
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Boultwood
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D002878:Chromosomes, Human, Pair 1; D002895:Chromosomes, Human, Pair 5; D002899:Chromosomes, Human, Pair 9; D004802:Eosinophilia / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009196:Myeloproliferative Disorders / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
chemical_list: D020797:Receptor, Platelet-Derived Growth Factor beta; D016044:Fusion Proteins, bcr-abl