MAPK pathway activation and the origins of pediatric low-grade astrocytomas.
Low-grade astrocytomas (LGAs) are the most common type of brain tumor in children. Until recently, very little was known about the underlying biology and molecular genetics of these tumors. However, within the past year a number of studies have shown that the MAPK pathway is constitutively activated in a high proportion of LGAs. Several genetic aberrations which generate this deregulation of the MAPK pathway have been identified, most notably gene fusions between KIAA1549 and BRAF. In this review we summarize these findings, discuss how these gene fusions may arise and consider possible implications for diagnosis and treatment.
Tatevossian
Ruth G
RG
Queen Mary University of London, Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK.
Lawson
Andrew R J
AR
Forshew
Tim
T
Hindley
Guy F L
GF
Ellison
David W
DW
Sheer
Denise
D
D000293:Adolescent; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020935:MAP Kinase Signaling System / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases