Aberrant signalling via platelet derived growth factor receptors (PDGFRs) and 
the RAS/MAPK pathway has been implicated in the development of medulloblastoma, 
the most common malignant brain tumour in childhood. To determine whether 
genetic mechanisms play a role in the activation of PDGFR-RAS/MAPK signalling in 
medulloblastoma, we performed a direct sequence analysis of the established 
mutational "hotspots" of known targets of activating mutations within the 
pathway (PDGFRA, NRAS, KRAS, HRAS and BRAF) and PDFRFB, in a cohort of 28 
primary tumours. A synonymous sequence variation in PDGFRA (CCG to CCA; PRO 567 
PRO) was detected in two cases (approximately 7%), but not in 150 normal 
chromosomes assessed, suggesting that the PDGFRA locus may be associated with 
medulloblastoma development in certain cases. No evidence for oncogenic 
mutations affecting NRAS, KRAS, HRAS, BRAF or PDFRFB was found in any case. 
These data demonstrate that activating mutations in established mutational 
hotspots within the PDGFR-RAS/MAPK pathway are rare events in medulloblastoma 
development, and suggest that alternative mechanisms are responsible for 
RAS/MAPK pathway activation in this disease.