Article
Analysis of the effect of 1p/19q co-deletions in WHO grade-II oligodendrogliomas
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Authors
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Özge Can
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey
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Aylin Mutlu
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey
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Sirin Yüksel
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey
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Yavuz Oktay
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey
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Cemaliye Akyerli
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey
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Paolo Nanni
- Functional Genomics Center Zurich, UZH/ETH Zurich, Zurich, Switzerland
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Nathalie Selevsek
- Functional Genomics Center Zurich, UZH/ETH Zurich, Zurich, Switzerland
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Jonas Grossmann
- Functional Genomics Center Zurich, UZH/ETH Zurich, Zurich, Switzerland
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Aysel Özpinar
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey
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Aydin Sav
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey
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Cengiz Yakicier
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey
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M. Necmettin Pamir
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey; Department of Neurosurgery, Acibadem University School of Medicine, Istanbul, Turkey
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Koray Özduman
- Acibadem University, Brain Tumor Research Center, Istanbul, Turkey; Department of Neurosurgery, Acibadem University School of Medicine, Istanbul, Turkey
| Published: | May 13, 2014 |
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Outline
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Objective: Among low-grade hemispheric gliomas, oligodendrogliomas have a relatively good prognosis. Oligodendrogliomas often carry 1p/19q co-deletions and the presence of this chromosomal change is associated with better prognosis and responsiveness to chemotherapy. Therefore the molecular biological changes associated with the 1p/19q co-deletion are of great interest. This study aims to compare the protein expression profile of 1p/19q co-deleted and non co-deleted oligodendrogliomas.
Method: 50 WHO grade-II oligodendrogliomas which were diagnosed by a single neuropathologist were analyzed for IDH1, IDH2, Olig-2, Ki67, EGFR, VEGF, pBRAF, c-myc, PTEN, p16Ink4A , TP53, MGMT methylation, 1p19q co-deletions, hTERT mutations were screened. 7 WHO grade-II oligodendrogliomas were included for the LC-MS/MS analysis. Tryptic digests of homogenized tissue extracts from 7 samples (5 patients with and 2 without 1p/19q codeletions) were analyzed by LC-MS/MS (LTQ-Orbitrap Velos ETD, Thermo Scientific) to analyze proteomic changes.
Results: After the analysis of the immunohistochemical and molecular biological markers in oligodendrogliomas, the most common pattern was that of oligodendrogliomas with (IDH mutation + 1p/19q co-deletions + hTERT promoter mutations + lost PTEN expression). In order to analyze the effects of 1p/19q co-deletions on the cellular proteome level more clearly, we have selected grade II oligodendrogliomas with or without 1p/19q co-deletions, which were all IDH mutant and lost PTEN protein expression. In the LC-MS/MS comparison of 5 codeleted oligodendrogliomas with 2 non-codeleted ones, 1601 proteins were identified with a false discovery rate of 0.2%. 116 proteins were found to be significantly regulated among the two groups (p<0.05), of which 14 of them have been associated with glioma previously. Granzyme A signaling (apoptosis and survival), cell adhesion and transcriptional silencing via heterochromatin protein 1 family were found to be the most significant pathways in the data set (p<0.0001). Correspondingly, the most important process networks for the proteomic data set were mRNA processing, chromatin modification, DNA damage/checkpoint (p<0.0001).
Conclusions: The presence of 1p/19q co-deletions are associated with different protein expression profiles in oligodendrogliomas.
