MAPK pathway activation and the origins of pediatric low-grade astrocytomas

J Cell Physiol. 2010 Mar;222(3):509-14. doi: 10.1002/jcp.21978.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Astrocytoma / enzymology*
  • Astrocytoma / genetics
  • Astrocytoma / pathology
  • Astrocytoma / therapy
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Child
  • Child, Preschool
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Gene Fusion
  • Humans
  • Infant
  • Infant, Newborn
  • MAP Kinase Signaling System* / genetics
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinases