| Full text | |
| Author(s): Show less - |
Bidinotto, Lucas Tadeu
[1, 2]
;
Torrieri, Raul
[1]
;
Mackay, Alan
[3, 4]
;
Almeida, Gisele Caravina
[5]
;
Viana-Pereira, Marta
[6, 7]
;
Cruvinel-Carloni, Adriana
[1]
;
Spina, Maria Luisa
[1, 2]
;
Campanella, Nathalia Cristina
[1]
;
de Menezes, Weder Pereira
[1]
;
Clara, Carlos Afonso
[8]
;
Becker, Aline Paixao
[1]
;
Jones, Chris
[3, 4]
;
Reis, Rui Manuel
[1, 6, 7]
Total Authors: 13
|
| Affiliation: | [1] Barretos Canc Hosp, Mol Oncol Res Ctr, Rua Antenor Duarte Villela 1331, BR-14784400 Sao Paulo - Brazil
[2] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, BR-14785002 Sao Paulo - Brazil
[3] Inst Canc Res, Div Mol Pathol, London SM2 5NG - England
[4] Inst Canc Res, Div Canc Therapeut, London SM2 5NG - England
[5] Barretos Canc Hosp, Dept Pathol, BR-14784400 Sao Paulo - Brazil
[6] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, P-4704553 Braga - Portugal
[7] 3Bs PT Govt Associate Lab, P-4704553 Braga - Portugal
[8] Barretos Canc Hosp, Dept Neurosurg, BR-14784400 Sao Paulo - Brazil
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | G3-GENES, GENOMES, GENETICS; v. 6, n. 7, p. 1867-1878, JUL 1 2016. |
| Web of Science Citations: | 2 |
| 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. (AU) | |
| FAPESP's process: | 12/08287-4 - Chromosomal alterations profiling in gliomas |
| Grantee: | Lucas Tadeu Bidinotto |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 11/08523-7 - Chromosomal alterations profiling in brain tumors (medulloblastomas and gliomas): the impact in the identification of new tumorigenic pathways |
| Grantee: | Lucas Tadeu Bidinotto |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 12/19590-0 - Mutational profile of glioblastoma primary cultures |
| Grantee: | Rui Manuel Vieira Reis |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/25787-3 - Study of biomarkers of prognosis and response to therapy in gastrointestinal stromal tumors (GISTs) |
| Grantee: | Nathália Cristina Campanella |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |