title: Molecular Diagnostic and Prognostic Subtyping of Gliomas in Tunisian Population.
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.
authors.affiliation: Department of Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Street Ibn Eljazzar, 4000, Sousse, Tunisia.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Trabelsi
authors.affiliation: Department of Medical Oncology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Chabchoub
authors.affiliation: Department of Neurosurgery, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Iadh
authors.initials: I
authors.lastname: Ksira
authors.affiliation: Department of Neurosurgery, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Nadhir
authors.initials: N
authors.lastname: Karmeni
authors.affiliation: Department of Imagery, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mama
authors.affiliation: Department of Radiotherapy, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Samia
authors.initials: S
authors.lastname: Kanoun
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Burford
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
authors.forename: Alexa
authors.initials: A
authors.lastname: Jury
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
authors.forename: Sergey
authors.initials: S
authors.lastname: Popov
authors.affiliation: Department of Radiotherapy, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Noureddine
authors.initials: N
authors.lastname: Bouaouina
authors.affiliation: Department of Medical Oncology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Slim
authors.initials: S
authors.lastname: Ben Ahmed
authors.affiliation: Department of Cytopathology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Moncef
authors.initials: M
authors.lastname: Mokni
authors.affiliation: Department of Imagery, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Kalthoum
authors.initials: K
authors.lastname: Tlili
authors.affiliation: Department of Neurosurgery, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Hedi
authors.initials: H
authors.lastname: Krifa
authors.affiliation: Department of Cytopathology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Mohamed Tahar
authors.initials: MT
authors.lastname: Yacoubi
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.affiliation: Department of Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Street Ibn Eljazzar, 4000, Sousse, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.affiliation: Department of Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Street Ibn Eljazzar, 4000, Sousse, Tunisia. dorrahmida@yahoo.fr.
authors.forename: Dorra
authors.initials: D
authors.lastname: H'mida Ben Brahim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D005910:Glioma / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D057089:Pathology, Molecular; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis; D014416:Tunisia; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: (Epi)genetic; Glioma; Molecular; Subtypes; Tunisia