The molecular landscape of glioma in patients with Neurofibromatosis 1

Research output: Contribution to journalArticlepeer-review

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The molecular landscape of glioma in patients with Neurofibromatosis 1. / D'Angelo, Fulvio; Ceccarelli, Michele; Tala; Garofano, Luciano; Zhang, Jing; Frattini, Véronique; Caruso, Francesca P; Lewis, Genevieve; Alfaro, Kristin D; Bauchet, Luc; Berzero, Giulia; Cachia, David; Cangiano, Mario; Capelle, Laurent; de Groot, John; DiMeco, Francesco; Ducray, François; Farah, Walid; Finocchiaro, Gaetano; Goutagny, Stéphane; Kamiya-Matsuoka, Carlos; Lavarino, Cinzia; Loiseau, Hugues; Lorgis, Véronique; Marras, Carlo E; McCutcheon, Ian; Nam, Do-Hyun; Ronchi, Susanna; Saletti, Veronica; Seizeur, Romuald; Slopis, John; Suñol, Mariona; Vandenbos, Fanny; Varlet, Pascale; Vidaud, Dominique; Watts, Colin; Tabar, Viviane; Reuss, David E; Kim, Seung-Ki; Meyronet, David; Mokhtari, Karima; Salvador, Hector; Bhat, Krishna P; Eoli, Marica; Sanson, Marc; Lasorella, Anna; Iavarone, Antonio.

In: Nature Medicine, Vol. 25, No. 1, 10.12.2018, p. 176-187.

Research output: Contribution to journalArticlepeer-review

Harvard

D'Angelo, F, Ceccarelli, M, Tala, Garofano, L, Zhang, J, Frattini, V, Caruso, FP, Lewis, G, Alfaro, KD, 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, CE, 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, DE, Kim, S-K, Meyronet, D, Mokhtari, K, Salvador, H, Bhat, KP, Eoli, M, Sanson, M, Lasorella, A & Iavarone, A 2018, 'The molecular landscape of glioma in patients with Neurofibromatosis 1', Nature Medicine, vol. 25, no. 1, pp. 176-187. https://doi.org/10.1038/s41591-018-0263-8

APA

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., ... Iavarone, A. (2018). The molecular landscape of glioma in patients with Neurofibromatosis 1. Nature Medicine, 25(1), 176-187. https://doi.org/10.1038/s41591-018-0263-8

Vancouver

D'Angelo F, Ceccarelli M, Tala, Garofano L, Zhang J, Frattini V et al. The molecular landscape of glioma in patients with Neurofibromatosis 1. Nature Medicine. 2018 Dec 10;25(1):176-187. https://doi.org/10.1038/s41591-018-0263-8

Author

D'Angelo, Fulvio ; Ceccarelli, Michele ; Tala ; Garofano, Luciano ; Zhang, Jing ; Frattini, Véronique ; Caruso, Francesca P ; Lewis, Genevieve ; Alfaro, Kristin D ; Bauchet, Luc ; Berzero, Giulia ; Cachia, David ; Cangiano, Mario ; Capelle, Laurent ; de Groot, John ; DiMeco, Francesco ; Ducray, François ; Farah, Walid ; Finocchiaro, Gaetano ; Goutagny, Stéphane ; Kamiya-Matsuoka, Carlos ; Lavarino, Cinzia ; Loiseau, Hugues ; Lorgis, Véronique ; Marras, Carlo E ; McCutcheon, Ian ; Nam, Do-Hyun ; Ronchi, Susanna ; Saletti, Veronica ; Seizeur, Romuald ; Slopis, John ; Suñol, Mariona ; Vandenbos, Fanny ; Varlet, Pascale ; Vidaud, Dominique ; Watts, Colin ; Tabar, Viviane ; Reuss, David E ; Kim, Seung-Ki ; Meyronet, David ; Mokhtari, Karima ; Salvador, Hector ; Bhat, Krishna P ; Eoli, Marica ; Sanson, Marc ; Lasorella, Anna ; Iavarone, Antonio. / The molecular landscape of glioma in patients with Neurofibromatosis 1. In: Nature Medicine. 2018 ; Vol. 25, No. 1. pp. 176-187.

Bibtex

@article{88e6d3c3c0e04c87b8eaeca98f69501c,
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.",
keywords = "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",
author = "Fulvio D'Angelo and Michele Ceccarelli and Tala and Luciano Garofano and Jing Zhang and V{\'e}ronique Frattini and Caruso, {Francesca P} and Genevieve Lewis and Alfaro, {Kristin D} and Luc Bauchet and Giulia Berzero and David Cachia and Mario Cangiano and Laurent Capelle and {de Groot}, John and Francesco DiMeco and Fran{\c c}ois Ducray and Walid Farah and Gaetano Finocchiaro and St{\'e}phane Goutagny and Carlos Kamiya-Matsuoka and Cinzia Lavarino and Hugues Loiseau and V{\'e}ronique Lorgis and Marras, {Carlo E} and Ian McCutcheon and Do-Hyun Nam and Susanna Ronchi and Veronica Saletti and Romuald Seizeur and John Slopis and Mariona Su{\~n}ol and Fanny Vandenbos and Pascale Varlet and Dominique Vidaud and Colin Watts and Viviane Tabar and Reuss, {David E} and Seung-Ki Kim and David Meyronet and Karima Mokhtari and Hector Salvador and Bhat, {Krishna P} and Marica Eoli and Marc Sanson and Anna Lasorella and Antonio Iavarone",
year = "2018",
month = dec,
day = "10",
doi = "10.1038/s41591-018-0263-8",
language = "English",
volume = "25",
pages = "176--187",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - The molecular landscape of glioma in patients with Neurofibromatosis 1

AU - D'Angelo, Fulvio

AU - Ceccarelli, Michele

AU - Tala, null

AU - Garofano, Luciano

AU - Zhang, Jing

AU - Frattini, Véronique

AU - Caruso, Francesca P

AU - Lewis, Genevieve

AU - Alfaro, Kristin D

AU - Bauchet, Luc

AU - Berzero, Giulia

AU - Cachia, David

AU - Cangiano, Mario

AU - Capelle, Laurent

AU - de Groot, John

AU - DiMeco, Francesco

AU - Ducray, François

AU - Farah, Walid

AU - Finocchiaro, Gaetano

AU - Goutagny, Stéphane

AU - Kamiya-Matsuoka, Carlos

AU - Lavarino, Cinzia

AU - Loiseau, Hugues

AU - Lorgis, Véronique

AU - Marras, Carlo E

AU - McCutcheon, Ian

AU - Nam, Do-Hyun

AU - Ronchi, Susanna

AU - Saletti, Veronica

AU - Seizeur, Romuald

AU - Slopis, John

AU - Suñol, Mariona

AU - Vandenbos, Fanny

AU - Varlet, Pascale

AU - Vidaud, Dominique

AU - Watts, Colin

AU - Tabar, Viviane

AU - Reuss, David E

AU - Kim, Seung-Ki

AU - Meyronet, David

AU - Mokhtari, Karima

AU - Salvador, Hector

AU - Bhat, Krishna P

AU - Eoli, Marica

AU - Sanson, Marc

AU - Lasorella, Anna

AU - Iavarone, Antonio

PY - 2018/12/10

Y1 - 2018/12/10

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Antigens, Neoplasm/metabolism

KW - Brain Neoplasms/complications

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - DNA Methylation/genetics

KW - Female

KW - Germ-Line Mutation/genetics

KW - Glioma/complications

KW - Humans

KW - Male

KW - Middle Aged

KW - Neurofibromatosis 1/complications

KW - Neurofibromin 1/genetics

KW - Reproducibility of Results

KW - T-Lymphocytes/immunology

KW - Transcriptome/genetics

KW - X-linked Nuclear Protein/genetics

KW - Young Adult

U2 - 10.1038/s41591-018-0263-8

DO - 10.1038/s41591-018-0263-8

M3 - Article

C2 - 30531922

VL - 25

SP - 176

EP - 187

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 1

ER -