Back to Search
Start Over
Molecular Diagnostic and Prognostic Subtyping of Gliomas in Tunisian Population
- Source :
- Molecular neurobiology. 54(4)
- Publication Year :
- 2015
-
Abstract
- It has become increasingly evident that morphologically similar gliomas may have distinct clinical phenotypes arising from diverse genetic signatures. To date, glial tumours from the Tunisian population have not been investigated. To address this, we correlated the clinico-pathology with molecular data of 110 gliomas by a combination of HM450K array, MLPA and TMA-IHC. PTEN loss and EGFR amplification were distributed in different glioma histological groups. However, 1p19q co-deletion and KIAA1549:BRAF fusion were, respectively, restricted to Oligodendroglioma and Pilocytic Astrocytoma. CDKN2A loss and EGFR overexpression were more common within high-grade gliomas. Furthermore, survival statistical correlations led us to identify Glioblastoma (GB) prognosis subtypes. In fact, significant lower overall survival (OS) was detected within GB that overexpressed EGFR and Cox2. In addition, IDH1R132H mutation seemed to provide a markedly survival advantage. Interestingly, the association of IDHR132H mutation and EGFR normal status, as well as the association of differentiation markers, defined GB subtypes with good prognosis. By contrast, poor survival GB subtypes were defined by the combination of PTEN loss with PDGFRa expression and/or EGFR amplification. Additionally, GB presenting p53-negative staining associated with CDKN2A loss or p21 positivity represented a subtype with short survival. Thus, distinct molecular subtypes with individualised prognosis were identified. Interestingly, we found a unique histone mutation in a poor survival young adult GB case. This tumour exceptionally associated the H3F3A G34R mutation and MYCN amplification as well as 1p36 loss and 10q loss. Furthermore, by exhibiting a remarkable methylation profile, it emphasised the oncogenic power of G34R mutation connecting gliomagenesis and chromatin regulation.
- Subjects :
- 0301 basic medicine
Male
Pathology
Kaplan-Meier Estimate
medicine.disease_cause
Epigenesis, Genetic
Cohort Studies
0302 clinical medicine
Cluster Analysis
Pathology, Molecular
Child
Mutation
Pilocytic astrocytoma
Brain Neoplasms
Glioma
Middle Aged
Prognosis
Phenotype
Immunohistochemistry
Neurology
030220 oncology & carcinogenesis
Child, Preschool
Female
Adult
medicine.medical_specialty
Tunisia
Adolescent
Neuroscience (miscellaneous)
PDGFRA
Biology
03 medical and health sciences
Cellular and Molecular Neuroscience
Young Adult
medicine
Biomarkers, Tumor
PTEN
Humans
Multiplex ligation-dependent probe amplification
neoplasms
Aged
Infant
DNA Methylation
medicine.disease
Survival Analysis
030104 developmental biology
Tissue Array Analysis
Cancer research
biology.protein
Oligodendroglioma
Subjects
Details
- ISSN :
- 15591182
- Volume :
- 54
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular neurobiology
- Accession number :
- edsair.doi.dedup.....9caf2b79ee360fe1f7225e33ff482bc5