Mutational analysis of PDGFR–RAS/MAPK pathway activation in childhood medulloblastoma
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 s...
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Published in | European journal of cancer (1990) Vol. 42; no. 5; pp. 646 - 649 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.03.2006
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0959-8049 1879-0852 |
DOI: | 10.1016/j.ejca.2005.11.023 |