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Proto-oncogene analyses in brain tumors
M Fujimoto1, P J Sheridan, Z D Sharp
1Department of Surgery, Division of Neurosurgery, University of Texas Health Science Center, San Antonio.
Abstract:
The present study determined which oncogenes (N-myc, c-myc, v-sis, or v-fos) were amplified and which messenger ribonucleic acids (mRNA's) accumulated in 10 primary human brain tumors of neuroectodermal origin. The tumors included four glioblastomas multiforme, one mixed glioma (astrocytoma grade I and ependymoma), one astrocytoma grade II, one cystic cerebellar astrocytoma, one ependymoma, one ganglioglioma, and one medulloblastoma. The relative amounts of polyadenylated (poly(A)+) RNA's homologous to these genes and their copy number were determined using the RNA and deoxyribonucleic acid blot hybridization techniques. The N-myc and v-sis probes hybridized strongly to the poly(A)+ RNA from the same recurrent glioblastoma with gene amplifications (N-myc 80 copies; v-sis three to four copies). The c-myc probe hybridized strongly to the recurrent medulloblastoma without gene amplification. The amplification or abundant accumulation of mRNA's homologous to their oncogenes may be involved in tumorigenesis or the aggressiveness of these malignant brain tumors of neuroectodermal origin and may be good molecular indicators of an extremely malignant state in these tumors.
Insights
This study investigated oncogene amplification and messenger RNA (mRNA) accumulation in human brain tumors. Findings suggest oncogene involvement in tumor aggressiveness and potential as malignancy indicators.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genetics
Background:
- Human brain tumors of neuroectodermal origin exhibit diverse genetic alterations.
- Oncogene amplification and aberrant mRNA expression are implicated in cancer development.
Purpose of the Study:
- To identify amplified oncogenes (N-myc, c-myc, v-sis, v-fos) and accumulated mRNAs in primary human brain tumors.
- To correlate oncogene status with tumor type and malignancy.
Main Methods:
- Analysis of 10 primary human brain tumors including glioblastomas, astrocytomas, ependymoma, ganglioglioma, and medulloblastoma.
- Utilized RNA and deoxyribonucleic acid blot hybridization techniques to determine gene copy number and polyadenylated (poly(A)+) RNA levels.
- Employed specific gene probes for N-myc, c-myc, v-sis, and v-fos.
Main Results:
- N-myc and v-sis gene amplifications (80 and 3-4 copies, respectively) correlated with strong mRNA hybridization in a recurrent glioblastoma.
- c-myc mRNA showed strong hybridization in a medulloblastoma without gene amplification.
- Tumor types analyzed included glioblastoma multiforme, mixed glioma, astrocytoma, ependymoma, ganglioglioma, and medulloblastoma.
Conclusions:
- Amplification or abundant mRNA accumulation of specific oncogenes may contribute to tumorigenesis and aggressiveness in neuroectodermal brain tumors.
- These molecular alterations could serve as indicators of a highly malignant tumor state.