The molecular landscape of glioma in patients with Neurofibromatosis 1
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
- BIOGEM Istituto di Ricerche Genetiche 'G. Salvatore', Ariano Irpino, Italy.
- Department of Science and Technology, Università degli Studi del Sannio, Benevento, Italy.
- Columbia University Medical Center
- The University of Texas M.D. Anderson Cancer Center John Mendelsohn Faculty Center (FC7.3025) - Neuro-Oncology - Unit 0431, Houston, TX, USA.
- University of Montpellier
- Sorbonne Universités UPMC Université Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, APHP, Paris, France.
- University of South Carolina
- AP-HP, Hôpital de la Pitié-Salpêtrière, Service de Neurochirurgie, Paris, France.
- Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
- Hunterian Brain Tumor Research Laboratory CRB2 2M41, Baltimore, MD, USA.
- Service de Neuro-Oncologie, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Department of Cancer Cell Plasticity, Cancer Research Center of Lyon, INSERM U1052, CNRS UMR5286, Lyon, France.
- Department of Neurosurgery, CHU, Dijon, France.
- Unit of Molecular Neuro-Oncology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy.
- Service de Neurochirurgie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
- Developmental Tumor Laboratory, Fundación Sant Joan de Déu, Barcelona, Spain.
- Department of Neurosurgery, Bordeaux University Hospital. Labex TRAIL (ANR-10-LABX-57). EA 7435 - IMOTION Bordeaux University, Bordeaux, France.
- Department of Medical Oncology, Centre GF Leclerc, Dijon, France.
- Pediatric Neurosurgery Unit, Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children's Hospital, Rome, Italy.
- Sungkyunkwan University
- Developmental Neurology Unit, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy.
- Service de Neurochirurgie, Hôpital de la Cavale Blanche, CHRU de Brest, Université de Brest, Brest, France.
- Department of Pathology, Hospital Sant Joan de Déu, Barcelona, Spain.
- Central Laboratory of Pathology, Pasteur I University Hospital, Nice, France.
- IMA-Brain, Inserm U894, Institute of Psychiatry and Neuroscience of Paris, Paris, France.
- AP-HP Hôpital Saint Antoine
- University of Birmingham
- Memorial Sloan Kettering Cancer Center
- Heidelberg University Hospital
- Seoul National University
- Centre de Pathologie Et Neuropathologie Est Hospices Civils de Lyon, Lyon, France.
- Pediatric Oncology Unit, Hospital Sant Joan de Déu, Esplugues, Barcelona, Spain.
- Columbia University
Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the prevalent tumors. Gliomagenesis in NF1 results in a heterogeneous spectrum of low- to high-grade neoplasms occurring during the entire lifespan of patients. The pattern of genetic and epigenetic alterations of glioma that develops in NF1 patients and the similarities with sporadic glioma remain unknown. Here, we present the molecular landscape of low- and high-grade gliomas in patients affected by NF1 (NF1-glioma). We found that the predisposing germline mutation of the NF1 gene was frequently converted to homozygosity and the somatic mutational load of NF1-glioma was influenced by age and grade. High-grade tumors harbored genetic alterations of TP53 and CDKN2A, frequent mutations of ATRX associated with Alternative Lengthening of Telomere, and were enriched in genetic alterations of transcription/chromatin regulation and PI3 kinase pathways. Low-grade tumors exhibited fewer mutations that were over-represented in genes of the MAP kinase pathway. Approximately 50% of low-grade NF1-gliomas displayed an immune signature, T lymphocyte infiltrates, and increased neo-antigen load. DNA methylation assigned NF1-glioma to LGm6, a poorly defined Isocitrate Dehydrogenase 1 wild-type subgroup enriched with ATRX mutations. Thus, the profiling of NF1-glioma defined a distinct landscape that recapitulates a subset of sporadic tumors.
|Number of pages||12|
|Publication status||Published - 10 Dec 2018|
- Adolescent, Adult, Antigens, Neoplasm/metabolism, Brain Neoplasms/complications, Child, Child, Preschool, Cohort Studies, DNA Methylation/genetics, Female, Germ-Line Mutation/genetics, Glioma/complications, Humans, Male, Middle Aged, Neurofibromatosis 1/complications, Neurofibromin 1/genetics, Reproducibility of Results, T-Lymphocytes/immunology, Transcriptome/genetics, X-linked Nuclear Protein/genetics, Young Adult