Artikel
IDH1 dependent chemical alterations in gliomas, and its implications for in situ optical diagnosis
Suche in Medline nach
Autoren
-
Wenmin Yao
- Klinik und Poliklinik für Neurochirurgie, Experimental Neuroimaging Laboratory, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
-
Ortrud Uckermann
- Klinik und Poliklinik für Neurochirurgie, Experimental Neuroimaging Laboratory, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
-
Tareq Juratli
- Klinik und Poliklinik für Neurochirurgie, Experimental Neuroimaging Laboratory, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
-
Roberta Galli
- Klinisches Sensoring und Monitoring, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
-
Elke Leipnitz
- Klinik und Poliklinik für Neurochirurgie, Experimental Neuroimaging Laboratory, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
-
Matthias Meinhardt
- Institut für Pathologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany
-
Gabriele Schackert
- Klinik und Poliklinik für Neurochirurgie, Experimental Neuroimaging Laboratory, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
-
Gerald Steiner
- Klinisches Sensoring und Monitoring, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
-
Matthias Kirsch
- Klinik und Poliklinik für Neurochirurgie, Experimental Neuroimaging Laboratory, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| Veröffentlicht: | 8. Juni 2016 |
|---|
Gliederung
Text
Objective: Mutation in isocitrate dehydrogenase1/-2 (IDH1, IDH2) genes have recently been identified as early and frequent genetic alterations in astrocytomas and secondary glioblastomas. The IDH1 mutation is associated with good prognosis. Based on these clinical findings, evaluating the IDH1 mutation status is thought to be of high importance in guiding treatment decisions in gliomas. Raman spectroscopy (RS) is a non-destructive biophotonic method that analyses the biochemical composition of cells and tissues. Here, we applied Raman spectroscopy to correlate biochemical alterations to their corresponding genotype with regards to IDH mutation status.
Method: Informed consent was obtained from 36 pts. harboring low-grade gliomas. 100 Raman spectra from cryosections of each sample were obtained using a Raman spectrometer (RamanRxn1, Kaiser Optical Systems Inc., Ann Arbor, USA) coupled to a light microscope. In addition, U7MG orthotopic gliomas in mice with various IDH-1 mutation / wild type genotypes were used as well. The neuropathological IDH-1/-2 mutation status was obtained by specific immunohistology and direct DNA sequencing. Statistical analysis of the complex data with 4000 data points per pixel and spectrum were performed in Matlab v7.2, using principle component analyses (PCA) and linear discriminant analyses (LDA) in an observed fashion, implying that the algorithm used the IDH mutations status as a classifier in a training set of 20 samples.
Results: Significant differences in the Raman spectra of IDH1/2 mutated tumors were found (p<0.05), particularly in the spectra ranges of 498 (nucleoc acids), 621, 642, 700, 720 (asymmetric stretching of choline group N+ (CH3)3 of phospholipids), 826, 961, 1003 (C-C ring breathing of Phenylalanine), 1173, 1337, 1440 (CH2 and CH3 groups in lipids), 1660cm-1 (C=C bonds in lipids). The PCA-LDA algorithms yielded an overall accuracy of 87% for distinguishing mut- from wt-IDH1/2 tumors in a separate test set containing 16 additional LGG, as well as in human U87 gliomas grown as orthotopic brain tumors in mice.
Conclusions: Raman spectroscopy provides a simple, rapid and low-cost procedure, based on the analyses of molecular signatures for determination of the IDH1 mutation status. It has the potential to be used as an online in vivo diagnostic method and opens the field for immediate consecutive personalized therapies in situ based on the specific molecular alteration as indicated by optical spectroscopy.
