1. Copy Number Profiling of Brazilian Astrocytomas.
- Author
-
Bidinotto LT, Torrieri R, Mackay A, Almeida GC, Viana-Pereira M, Cruvinel-Carloni A, Spina ML, Campanella NC, Pereira de Menezes W, Clara CA, Becker AP, Jones C, and Reis RM
- Subjects
- Adolescent, Adult, Aged, Astrocytoma diagnosis, Astrocytoma metabolism, Astrocytoma pathology, Brain Neoplasms diagnosis, Brain Neoplasms metabolism, Brain Neoplasms pathology, Brazil, Child, Comparative Genomic Hybridization, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p18 genetics, Cyclin-Dependent Kinase Inhibitor p18 metabolism, ErbB Receptors genetics, ErbB Receptors metabolism, Female, Glioblastoma diagnosis, Glioblastoma metabolism, Glioblastoma pathology, Humans, Isocitrate Dehydrogenase genetics, Isocitrate Dehydrogenase metabolism, Male, Microsatellite Instability, Middle Aged, Neoplasm Grading, Neoplasm Proteins metabolism, PTEN Phosphohydrolase genetics, PTEN Phosphohydrolase metabolism, Proto-Oncogene Proteins c-kit genetics, Proto-Oncogene Proteins c-kit metabolism, Proto-Oncogene Proteins c-met genetics, Proto-Oncogene Proteins c-met metabolism, Receptor, Platelet-Derived Growth Factor alpha genetics, Receptor, Platelet-Derived Growth Factor alpha metabolism, Telomerase genetics, Telomerase metabolism, Tissue Array Analysis, Vascular Endothelial Growth Factor Receptor-2 genetics, Vascular Endothelial Growth Factor Receptor-2 metabolism, Astrocytoma genetics, Brain Neoplasms genetics, Gene Dosage, Gene Expression Regulation, Neoplastic, Glioblastoma genetics, Neoplasm Proteins genetics
- Abstract
Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of distinct malignant grades (WHO grade I-IV) of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI), and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM), the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET) and deletions (CDKN2A and PTEN) Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7%) and anaplastic (100%) astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas., (Copyright © 2016 Bidinotto et al.)
- Published
- 2016
- Full Text
- View/download PDF