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Molecular genetic alterations in radiation-induced astrocytomas
D J Brat1, C D James, A E Jedlicka
1Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland, USA. dbrat@pds.path.jhu.edu
The American Journal of Pathology
|May 18, 1999
Summary
Radiation-induced astrocytomas in the central nervous system show high-grade histology. Molecular genetic alterations in these tumors are similar to spontaneous high-grade astrocytomas, not a unique subset.
Area of Science:
- Neuro-oncology
- Radiation oncology
- Molecular genetics
Background:
- Astrocytic tumors can develop in the central nervous system after radiotherapy.
- The molecular genetic profile of these postradiation gliomas is not well-defined.
Purpose of the Study:
- To investigate the molecular genetic characteristics of astrocytomas that arise after radiotherapy.
- To determine if these tumors represent a distinct molecular subset.
Main Methods:
- Analysis of nine postradiation astrocytoma cases.
- DNA sequencing and quantitative PCR for genes including p53, PTEN, K-ras, EGFR, MTAP, and p16.
- Immunohistochemistry for p53 and EGFR.
Main Results:
- EGFR gene amplification in 2 of 8 tumors.
- Chromosome 9p deletions (including p16 and MTAP) in 2 of 7 and 3 of 7 tumors, respectively.
- p53 mutations found in only 1 of 9 cases; no PTEN mutations identified.
Conclusions:
- Postradiation astrocytomas present with high histological grade.
- The molecular genetic alterations observed are similar to spontaneous high-grade astrocytomas.
- These tumors do not appear to represent a unique molecular genetic subset.