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Mutation Screening of Her-2, N-ras and Nf1 Genes in Brain Tumor Biopsies
Christos Yapijakis1, Maria Adamopoulou2, Konstantina Tasiouka2
11st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece cyapi@med.uoa.gr.
Background/Aim:
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.
Materials And Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Activated N-ras mutations are common in brain tumors, playing a key role in oncogenesis. This study investigated the her-2 (erbB-2/neu/ngl)/N-ras/nf1 pathway in various brain tumor specimens.
Area of Science:
- Neuro-oncology
- Molecular pathology
- Cancer genetics
Background:
- Brain malignancies require better targeted therapies.
- Understanding the molecular pathology of brain oncogenesis is crucial.
- The her-2 (erbB-2/neu/ngl)/N-ras/nf1 pathway is implicated in brain tumor development.
Purpose of the Study:
- To investigate the molecular pathology of brain oncogenesis.
- To screen genotypes of brain tumor specimens within the her-2/N-ras/nf1 pathway.
- To identify common mutations in oncogenes and tumor suppressor genes.
Main Methods:
- Analysis of 35 brain tumor biopsies including neuroglial, meningiomas, other nervous system, and metastatic tumors.
- Screening for mutations using molecular hybridization techniques (Southern blotting, dot blot, SSCP).
- Confirmation of mutations via DNA sequencing.
Main Results:
- Her-2 gene amplification was found in 6% of cases (glioblastoma, meningioma).
- N-ras mutations occurred in 54% of biopsies across all tumor categories.
- A novel nf1 gene mutation was identified in a glioblastoma case.
Conclusions:
- Activated N-ras mutations are prevalent in brain tumors.
- N-ras plays a significant role as an oncogene in brain oncogenesis.
- The her-2/N-ras/nf1 pathway is important in the development of brain tumors.
