Further evidence for a somatic KRAS mutation in a pilocytic astrocytoma.
Astrocytomas are the most common brain tumors of childhood. However, knowledge of the molecular etiology of astrocytomas WHO grade I and II is limited. Germline mutations in the Ras-guanosine triphosphatase-activating protein, neurofibromin, in individuals with neurofibromatosis type I predispose to pilocytic astrocytomas. This association suggests that constitutive activation of the Ras signaling pathway plays a fundamental role in astrocytoma development. We screened 25 WHO I and II astrocytomas for mutations of PTPN11, NRAS, KRAS, and HRAS genes and identified the somatic G12A KRAS mutation in one pilocytic astrocytoma. These data suggest that Ras is rarely mutated in these tumors. Analyzed astrocytomas without mutations in Ras or neurofibromin may harbor mutations in other proteins of this pathway leading to hyperactive Ras signaling.
Janzarik
W G
WG
Department of Neurology, University Hospital Freiburg, Freiburg, Germany.
Kratz
C P
CP
Loges
N T
NT
Olbrich
H
H
Klein
C
C
Schäfer
T
T
Scheurlen
W
W
Roggendorf
W
W
Weiller
C
C
Niemeyer
C
C
Korinthenberg
R
R
Pfister
S
S
Omran
H
H
D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D005091:Exons / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins