The molecular landscape of glioma in patients with neurofibromatosis 1 Journal Article
| Authors: | D’Angelo, F.; Ceccarelli, M.; Tala; Garofano, L.; Zhang, J.; Frattini, V.; Caruso, F. P.; Lewis, G.; Alfaro, K. D.; Bauchet, L.; Berzero, G.; Cachia, D.; Cangiano, M.; Capelle, L.; de Groot, J.; DiMeco, F.; Ducray, F.; Farah, W.; Finocchiaro, G.; Goutagny, S.; Kamiya-Matsuoka, C.; Lavarino, C.; Loiseau, H.; Lorgis, V.; Marras, C. E.; McCutcheon, I.; Nam, D. H.; Ronchi, S.; Saletti, V.; Seizeur, R.; Slopis, J.; Suñol, M.; Vandenbos, F.; Varlet, P.; Vidaud, D.; Watts, C.; Tabar, V.; Reuss, D. E.; Kim, S. K.; Meyronet, D.; Mokhtari, K.; Salvador, H.; Bhat, K. P.; Eoli, M.; Sanson, M.; Lasorella, A.; Iavarone, A. |
| Article Title: | The molecular landscape of glioma in patients with neurofibromatosis 1 |
| Abstract: | 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. © 2018, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | immunohistochemistry; adolescent; adult; child; controlled study; human tissue; aged; human cell; major clinical study; promoter region; single nucleotide polymorphism; somatic mutation; missense mutation; glioma; allele; homologous recombination; cancer susceptibility; gene overexpression; cell infiltration; cohort analysis; fibroblast growth factor receptor 3; phosphatidylinositol 3 kinase; protein p53; dna methylation; double stranded dna; transcription regulation; epigenetics; chromatin; telomerase reverse transcriptase; neurofibromin; dna sequence; cyclin dependent kinase inhibitor 2a; genetic predisposition; cell activation; genomic dna; complementary dna; chromatin assembly and disassembly; rna sequence; genetic algorithm; molecular pathology; copy number variation; isocitrate dehydrogenase 1; neurofibromatosis type 1; germline mutation; gene ontology; indel mutation; fibroblast growth factor 1; sanger sequencing; human; male; female; priority journal; article; whole exome sequencing; transcriptional regulator atrx |
| Journal Title: | Nature Medicine |
| Volume: | 25 |
| Issue: | 1 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-01-01 |
| Start Page: | 176 |
| End Page: | 187 |
| Language: | English |
| DOI: | 10.1038/s41591-018-0263-8 |
| PUBMED: | 30531922 |
| PROVIDER: | scopus |
| PMCID: | PMC6857804 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2019 -- Source: Scopus |
