RSS-Feed abonnieren
DOI: 10.1055/s-2007-984451
© Georg Thieme Verlag KG Stuttgart · New York
Further Evidence for a Somatic KRAS Mutation in a Pilocytic Astrocytoma
Publikationsverlauf
received 15.3.2007
accepted 15.5.2007
Publikationsdatum:
22. August 2007 (online)
Abstract
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.
Key words
Astrocytoma - RAS - tumor
References
- 1 Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K. et al . Activating mutations of the Noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res. 2004; 64 8816-8820
- 2 Bentires-Alj M, Kontaridis MI, Neel BG. Stops along the RAS pathway in human genetic disease. Nat Med. 2006; 12 283-285
- 3 Bos JL, Fearon ER, Hamilton SR, Verlaan-de Vries M, Boom JH, Eb AJ. et al . Prevalence of ras gene mutations in human colorectal cancers. Nature. 1987; 327 293-297
- 4 Burmer GC, Rabinovitch PS, Loeb LA. Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma. Environ Health Perspect. 1991; 93 27-31
- 5 Collins VP. Brain tumours: classification and genes. J Neurol Neurosurg Psychiatry. 2004; 75 ((Suppl 2)) ii2-11
- 6 Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S. et al . Mutations of the BRAF gene in human cancer. Nature. 2002; 417 949-954
- 7 Emanuel PD. Juvenile myelomonocytic leukemia. Curr Hematol Rep. 2004; 3 203-209
- 8 Flotho C, Valcamonica S, Mach-Pascual S, Schmahl G, Corral L, Ritterbach J. et al . RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia. 1999; 13 32-37
- 9 Lau N, Feldkamp MM, Roncari L, Loehr AH, Shannon P, Gutmann DH. et al . Loss of neurofibromin is associated with activation of RAS/MAPK and PI3-K/AKT signaling in a neurofibromatosis 1 astrocytoma. J Neuropathol Exp Neurol. 2000; 59 759-767
- 10 Sanford RA, Bowman R, Tomita T, Leon G, Palka P. A 16-year-old male with Noonan's syndrome develops progressive scoliosis and deteriorating gait. Pediatr Neurosurg. 1999; 30 47-52
- 11 Sharma MK, Zehnbauer BA, Watson MA, Gutmann DH. RAS pathway activation and an oncogenic RAS mutation in sporadic pilocytic astrocytoma. Neurology. 2005; 65 1335-1336
- 12 Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A. et al . Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet. 2003; 34 148-150
- 13 Boom J, Wolter M, Kuick R, Misek DE, Youkilis AS, Wechsler DS. et al . Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. Am J Pathol. 2003; 163 1033-1043
Correspondence
Prof. Dr. H. Omran
Department of Pediatric Neurology and Muscle Disorders
University Hospital Freiburg
Mathildenstr. 1
79106 Freiburg
Germany
Telefon: +49/761/270 43 65
Fax: +49/761/270 43 65
eMail: heymut.omran@uniklinik-freiburg.de