Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis.
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.
Erben
Philipp
P
III. Medizinische Klinik, Universitätsmedizin Mannheim Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Gosenca
Darko
D
Müller
Martin C
MC
Reinhard
Jelena
J
Score
Joannah
J
Del Valle
Francesco
F
Walz
Christoph
C
Mix
Jürgen
J
Metzgeroth
Georgia
G
Ernst
Thomas
T
Haferlach
Claudia
C
Cross
Nicholas C P
NC
Hochhaus
Andreas
A
Reiter
Andreas
A
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
D015514:Oncogene Proteins, Fusion; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta