Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation.
BACKGROUND
Mutations involving KIT and FLT3 genes, encoding tyrosine kinase (TK) membrane receptors, are detected in core-binding factor leukaemia (CBFL) patients. PDFGRA and PDGFRB encode class III TK receptors and are involved both in physiological processes and in the pathogenesis of haematological and solid tumours. The aim of this study was to investigate if PDGFR mutations are involved in CBFL.


METHODS
In order to detect PDGFR mutations in CBFL, 35 patients without KIT or FLT3 mutations patients were screened by rapid and sensitive single-strand conformation polymorphism (SSCP) analysis. Sequence analysis was performed in polymerase chain reaction (PCR) products showing altered mobility in SSCP analysis in order to determine the nucleotide changes.


RESULTS
Three types of single-nucleotide polymorphism (SNP) were detected in the PDGFRA gene (exon 12, exon 13 and exon 18) while no mutation of PDGFRB was detected in the tested CBFLs.


CONCLUSIONS
These data showed that no pathogenic mutations in PDGFRA and PDGFRB were detected in the context of CBFL without KIT and FLT3 mutations. Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients.
Trojani
Alessandra
A
Division of Hematology, Niguarda Hospital, Milan, Italy. alessandra.trojani@ospedaleniguarda.it
Ripamonti
Carla Barbara
CB
Penco
Silvana
S
Beghini
Alessandro
A
Nadali
Gianpaolo
G
Di Bona
Eros
E
Viola
Assunta
A
Castagnola
Carlo
C
Colapietro
Patrizia
P
Grillo
Giovanni
G
Pezzetti
Laura
L
Ravelli
Erica
E
Patrosso
Maria Cristina
MC
Marocchi
Alessandro
A
Cuneo
Antonio
A
Ferrara
Felicetto
F
Lazzarino
Mario
M
Pizzolo
Giovanni
G
Cairoli
Roberto
R
Morra
Enrica
E
D000208:Acute Disease; D000328:Adult; D000368:Aged; D050660:Core Binding Factors / Q000235:genetics; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D050660:Core Binding Factors; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D051941:fms-Like Tyrosine Kinase 3