7 results on '"Carpentier C"'
Search Results
2. Tumor cells with neuronal intermediate progenitor features define a subgroup of 1p/19q co-deleted anaplastic gliomas.
- Author
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Bielle F, Ducray F, Mokhtari K, Dehais C, Adle-Biassette H, Carpentier C, Chanut A, Polivka M, Poggioli S, Rosenberg S, Giry M, Marie Y, Duyckaerts C, Sanson M, Figarella-Branger D, and Idbaih A
- Subjects
- Adult, Chromosome Deletion, Computational Biology, Female, Humans, Male, Middle Aged, Neural Stem Cells metabolism, Neurogenesis, Phenotype, Repressor Proteins metabolism, Retrospective Studies, SOX9 Transcription Factor metabolism, Brain Neoplasms genetics, Brain Neoplasms pathology, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Neural Stem Cells pathology, Oligodendroglioma genetics, Oligodendroglioma pathology
- Abstract
The integrated diagnosis of anaplastic oligodendroglioma, IDH mutant and 1p/19q co-deleted, grade III (O3
id ) is a histomolecular entity that WHO 2016 classification distinguished from other diffuse gliomas by specific molecular alterations. In contrast, its cell portrait is less well known. The present study is focused on intertumor and intratumor, cell lineage-oriented, heterogeneity in O3id . Based on pathological, transcriptomic and immunophenotypic studies, a novel subgroup of newly diagnosed O3id overexpressing neuronal intermediate progenitor (NIP) genes was identified. This NIP overexpression pattern in O3id is associated with: (i) morphological and immunohistochemical similarities with embryonic subventricular zone, (ii) proliferating tumor cell subpopulation with NIP features including expression of INSM1 and no expression of SOX9, (iii) mutations in critical genes involved in NIP biology and, (iv) increased tumor necrosis. Interestingly, NIP tumor cell subpopulation increases in O3id recurrence compared with paired newly diagnosed tumors. Our results, validated in an independent cohort, emphasize intertumor and intratumor heterogeneity in O3id and identified a tumor cell subpopulation exhibiting NIP characteristics that is potentially critical in oncogenesis of O3id . A better understanding of spatial and temporal intratumor cell heterogeneity in O3id will open new therapeutic avenues overcoming resistance to current antitumor treatments., (© 2016 International Society of Neuropathology.)- Published
- 2017
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3. Mitotic index, microvascular proliferation, and necrosis define 3 pathological subgroups of prognostic relevance among 1p/19q co-deleted anaplastic oligodendrogliomas.
- Author
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Figarella-Branger D, Mokhtari K, Dehais C, Carpentier C, Colin C, Jouvet A, Uro-Coste E, Forest F, Maurage CA, Vignaud JM, Polivka M, Lechapt-Zalcman E, Eimer S, Viennet G, Quintin-Roué I, Aubriot-Lorton MH, Diebold MD, Loussouarn D, Lacroix C, Rigau V, Laquerrière A, Vandenbos F, Michalak S, Sevestre H, Peoch M, Labrousse F, Christov C, Kemeny JL, Chenard MP, Chiforeanu D, Ducray F, Idbaih A, and Delattre JY
- Subjects
- Brain Neoplasms blood supply, Brain Neoplasms genetics, Female, Humans, Isocitrate Dehydrogenase genetics, Male, Middle Aged, Necrosis, Oligodendroglioma blood supply, Oligodendroglioma genetics, Prognosis, Survival Rate, Brain Neoplasms pathology, Chromosome Deletion, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 19 genetics, Mitotic Index, Neovascularization, Pathologic, Oligodendroglioma pathology
- Published
- 2016
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4. Integrated multi-omics analysis of oligodendroglial tumours identifies three subgroups of 1p/19q co-deleted gliomas.
- Author
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Kamoun A, Idbaih A, Dehais C, Elarouci N, Carpentier C, Letouzé E, Colin C, Mokhtari K, Jouvet A, Uro-Coste E, Martin-Duverneuil N, Sanson M, Delattre JY, Figarella-Branger D, de Reyniès A, and Ducray F
- Subjects
- Adult, Aged, Aged, 80 and over, Cluster Analysis, Female, Gene Expression Profiling methods, Glioma genetics, Humans, Male, Middle Aged, Neurons metabolism, Oligodendroglia metabolism, Proto-Oncogene Proteins c-myc genetics, Signal Transduction genetics, Stem Cells metabolism, Survival Analysis, Young Adult, Chromosome Deletion, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 19 genetics, DNA Methylation, Genomics, Oligodendroglioma genetics, Transcriptome
- Abstract
Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished on the basis of the IDH mutation and 1p/19q co-deletion. Here we present an integrated analysis of the transcriptome, genome and methylome of 156 OT. Not only does our multi-omics classification match the current classification but also reveals three subgroups within 1p/19q co-deleted tumours, associated with specific expression patterns of nervous system cell types: oligodendrocyte, oligodendrocyte precursor cell (OPC) and neuronal lineage. We confirm the validity of these three subgroups using public datasets. Importantly, the OPC-like group is associated with more aggressive clinical and molecular patterns, including MYC activation. We show that the MYC activation occurs through various alterations, including MYC genomic gain, MAX genomic loss, MYC hypomethylation and microRNA-34b/c down-regulation. In the lower grade glioma TCGA dataset, the OPC-like group is associated with a poorer outcome independently of histological grade. Our study reveals previously unrecognized heterogeneity among 1p/19q co-deleted tumours.
- Published
- 2016
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5. Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations.
- Author
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Figarella-Branger D, Mokhtari K, Dehais C, Jouvet A, Uro-Coste E, Colin C, Carpentier C, Forest F, Maurage CA, Vignaud JM, Polivka M, Lechapt-Zalcman E, Eimer S, Viennet G, Quintin-Roué I, Aubriot-Lorton MH, Diebold MD, Loussouarn D, Lacroix C, Rigau V, Laquerrière A, Vandenbos F, Michalak S, Sevestre H, Peoch M, Labrousse F, Christov C, Kemeny JL, Chenard MP, Chiforeanu D, Ducray F, and Idbaih A
- Subjects
- Brain blood supply, Brain pathology, Brain Neoplasms complications, Disease-Free Survival, Humans, Isocitrate Dehydrogenase genetics, Mitotic Index, Necrosis complications, Neovascularization, Pathologic complications, Oligodendroglioma complications, Brain Neoplasms genetics, Brain Neoplasms pathology, Chromosome Deletion, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 19 genetics, Oligodendroglioma genetics, Oligodendroglioma pathology
- Abstract
Background: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs)., Methods: The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing., Results: 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10(-4)), IDH1/2 mutation (P < 10(-4)), chromosome 4 loss (P < 10(-3)), and better overall survival (P < 10(-4)). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023)., Conclusions: The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2014
- Full Text
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6. Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression.
- Author
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Reyes-Botero G, Dehais C, Idbaih A, Martin-Duverneuil N, Lahutte M, Carpentier C, Letouzé E, Chinot O, Loiseau H, Honnorat J, Ramirez C, Moyal E, Figarella-Branger D, and Ducray F
- Subjects
- Adult, Aged, Brain Neoplasms genetics, Chromosomes, Human, Pair 9, Female, Gene Expression, Genomic Instability, Humans, Isocitrate Dehydrogenase genetics, Male, Middle Aged, Mutation, Neovascularization, Pathologic genetics, Oligodendroglioma genetics, Polymorphism, Single Nucleotide, Young Adult, Brain Neoplasms pathology, Chromosome Deletion, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 19 genetics, Magnetic Resonance Imaging, Oligodendroglioma pathology
- Abstract
Background: The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs)., Methods: The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays., Results: Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2., Conclusion: In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.
- Published
- 2014
- Full Text
- View/download PDF
7. Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas.
- Author
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Alentorn A, van Thuijl HF, Marie Y, Alshehhi H, Carpentier C, Boisselier B, Laigle-Donadey F, Mokhtari K, Scheinin I, Wesseling P, Ylstra B, Capelle L, Hoang-Xuan K, Sanson M, Delattre JY, Reijneveld JC, and Idbaih A
- Subjects
- Adult, Brain Neoplasms genetics, Chromosomes, Human, Pair 1 genetics, Female, Glioblastoma genetics, Humans, Male, Middle Aged, Survival Analysis, Brain Neoplasms diagnosis, Chromosome Deletion, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 19 genetics, Glioblastoma diagnosis
- Abstract
Background: Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs., Methods: We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis., Results: Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs., Conclusion: Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.
- Published
- 2014
- Full Text
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