title: Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis.
abstract: BACKGROUND
  Rapid identification of diverse fusion genes with involvement of PDGFRA or PDGFRB in eosinophilia-associated myeloproliferative neoplasms is essential for adequate clinical management but is complicated by the multitude and heterogeneity of partner genes and breakpoints.
  
  
  METHODS
  We established a generic quantitative reverse transcriptase polymerase chain reaction to detect overexpression of the 3'-regions of PDGFRA or PDGFRB as a possible indicator of an underlying fusion.
  
  
  RESULTS
  At diagnosis, all patients with known fusion genes involving PDGFRA (n=5; 51 patients) or PDGFRB (n=5; 7 patients) showed significantly increased normalized expression levels compared to 191 patients with fusion gene-negative eosinophilia or healthy individuals (PDGFRA/ABL: 0.73 versus 0.0066 versus 0.0064, P<0.0001; PDGFRB/ABL: 196 versus 3.8 versus 5.85, P<0.0001). The sensitivity and specificity of the activation screening test were, respectively, 100% and 88.4% for PDGFRA and 100% and 94% for PDGFRB. Furthermore, significant overexpression of PDGFRB was found in a patient with an eosinophilia-associated myeloproliferative neoplasm with uninformative cytogenetics and an excellent response to imatinib. Subsequently, a new SART3-PDGFRB fusion gene was identified by 5'-rapid amplification of cDNA ends polymerase chain reaction (5'-RACE-PCR).
  
  
  CONCLUSIONS
  Quantitative reverse transcriptase polymerase chain reaction analysis is a simple and useful adjunct to standard diagnostic assays to detect clinically significant overexpression of PDGFRA and PDGFRB in eosinophilia-associated myeloproliferative neoplasms or related disorders.
authors.affiliation: III. Medizinische Klinik, Universitätsmedizin Mannheim Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Erben
authors.forename: Darko
authors.initials: D
authors.lastname: Gosenca
authors.forename: Martin C
authors.initials: MC
authors.lastname: Müller
authors.forename: Jelena
authors.initials: J
authors.lastname: Reinhard
authors.forename: Joannah
authors.initials: J
authors.lastname: Score
authors.forename: Francesco
authors.initials: F
authors.lastname: Del Valle
authors.forename: Christoph
authors.initials: C
authors.lastname: Walz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Mix
authors.forename: Georgia
authors.initials: G
authors.lastname: Metzgeroth
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004802:Eosinophilia / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta