Toggle Main Menu Toggle Search

Open Access padlockePrints

Mutational analysis of PDGFR-RAS/MAPK pathway activation in childhood medulloblastoma

Lookup NU author(s): Dr Richard Gilbertson, Dr Jackie Langdon, Roberto Hernan, Professor Steven Clifford

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

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 (∼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. © 2005 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Gilbertson R, Langdon J, Hollander A, Hernan R, Hogg T, Gajjar A, Fuller C, Clifford SC

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer

Year: 2006

Volume: 42

Issue: 5

Pages: 646-649

Print publication date: 01/03/2006

ISSN (print): 0959-8049

ISSN (electronic): 1879-0852

URL: http://dx.doi.org/10.1016/j.ejca.2005.11.023

DOI: 10.1016/j.ejca.2005.11.023

PubMed id: 16434186


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
CA21765NCI NIH HHS
CA96832-01NCI NIH HHS
R25 CA023944NCI NIH HHS

Share