Artikel
Management of gliomas based on the genetic profiles
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Autoren
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Y. Hirose
- Department of Neurosurgery, Fujita Health University, Toyoake, Japan
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H. Sasaki
- Department of Neurosurgery, Keio University, Tokyo, Japan
| Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: Management of gliomas depends on the histological diagnosis based on the morphology of the cells that are thought to represent the origin of the disease. However, there are limitations to the systems presently used to define these tumors. The tumors in the same entity could show varied clinical courses, especially when they are diagnosed as WHO grade II-III. Recently, various studies have revealed that genetic analyses of gliomas can provide clinically relevant information, and we aimed to develop genetic subgrouping of gliomas in an effort to establish treatment protocols based on the genetic background of the tumors.
Methods: We analyzed the chromosomal copy number aberrations of 150 adult supratentorial gliomas using comparative genomic hybridization (CGH) method. Tumor DNA was extracted from microdissected tissue sections. We classified the tumors analyzed into subgroups according to chromosomal copy number aberrations. We also investigated the mutational status of IDH1 by PCR-based direct sequencing and its correlation to CGH data. The genetic profiles were analyzed for their significance in terms of clinical relevance.
Results: The tumors were classified into subgroups on the basis of genetic profiles as follows; tumors with a gain on chromosome arm 7q (+7q), tumors with a gain of a whole chromosome 7 (+7), tumors with a gain of 7 and loss of 10q (+7/-10q), tumors with -1p, tumors with -1p/+7, tumors with other aberrations, and tumors without any aberrations. WHO grade II-III gliomas contained a variety of genetic subgroups that correlated well with the clinical course. Of these, tumors with +7q and those with -1p/19q, low grade tumors of 2 major lineages, showed long PFS which was undefined in our analysis. Cox regression multivariate analysis revealed that the PFS of +7q group was significantly longer than that of +7p or +7/-10q groups. Furthermore, all +7q tumors were IDH1 mutant whereas the great majority of +7p or +7/-10q groups had wildtype IDH1.
Conclusions: Our data suggest that cytogenetic characterization may provide an additional classification system for gliomas. Furthermore, we found +7q tumors were a distinct tumor lineage from tumors with whole 7 gain. In conclusion we believe genetic criteria could help to establish rational and objective means for analyzing treatment protocols.
