title: Mutation Screening of Her-2, N-ras and Nf1 Genes in Brain Tumor Biopsies.
abstract: A deeper understanding of the complex molecular pathology of brain malignancies is needed in order to develop more effective and targeted therapies of these highly lethal disorders. In an effort to further enlighten the molecular pathology of brain oncogenesis involving the her-2 (erbB-2/neu/ngl)/N-ras/nf1 pathway, we screened the genotypes of specimens from various types of brain tumors.
  
  
  
  The studied specimens included 35 biopsies of four general categories: 13 neuroglial tumors (4 astrocytomas, 2 oligodendrogliomas, 7 glioblastomas multiforme), 14 meningiomas, 3 other nervous system tumors (2 schwannomas, 1 craniopharyngioma) and 5 metastatic tumors (such as lung carcinomas and chronic myelocytic leukemia). Screening for most common mutations in oncogenes her-2, N-ras and tumor suppressor gene nf1 was conducted with molecular hybridization techniques (Southern blotting, dot blot and single-strand conformational polymorphism (SSCP) analysis, respectively), and was confirmed by DNA sequencing.
  
  
  
  Gene amplification of her-2 was observed in only two cases (6%), namely in one glioblastoma and in one meningioma. Screening of 3 hot spot codons of the N-ras gene (12, 13 and 61) and subsequent DNA sequencing revealed mutations in 19 biopsies encompassing all categories (54%). Screening for mutations in exons of the nf1 gene by SSCP analysis detected a novel nonsense mutation in exon 31 in a unique case of a glioblastoma biopsy (3%) taken from a patient without neurofibromatosis type I.
  
  
  
  Activated N-ras appears to be a major oncogene in brain oncogenesis, exhibiting the most important role in the her-2/N-ras/nf1 pathway.
authors.affiliation: 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece cyapi@med.uoa.gr.
authors.forename: Christos
authors.initials: C
authors.lastname: Yapijakis
authors.affiliation: 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Adamopoulou
authors.affiliation: 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Tasiouka
authors.affiliation: 2nd Department of Neurology, University of Athens Medical School, Attikon Hospital, Athens, Greece.
authors.forename: Costas
authors.initials: C
authors.lastname: Voumvourakis
authors.affiliation: 1st Department of Neurosurgery, University of Athens Medical School, Evangelismos Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Stranjalis
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001932:Brain Neoplasms / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism*; D003062:Codon; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016514:Genes, Neurofibromatosis 1; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D025542:Neurofibromin 1 / Q000378:metabolism*; D018807:Polymorphism, Single-Stranded Conformational; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D003062:Codon; D025542:Neurofibromin 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C508053:ERBB2 protein, human
keywords: Mutation screening; N-ras; brain tumors; her-2; nf1; oncogenes