The molecular landscape of glioma in patients with Neurofibromatosis 1
Fulvio d'Angelo
(1)
,
Michele Ceccarelli
(2)
,
Dr Tala
(1)
,
Luciano Garofano
(1)
,
Jing Zhang
(1)
,
Véronique Frattini
(1)
,
Francesca P Caruso
(2)
,
Genevieve Lewis
(1)
,
Kristin D Alfaro
(3)
,
Luc Bauchet
(4, 5)
,
Giulia Berzero
(6, 7, 8)
,
David Cachia
(9)
,
Mario Cangiano
,
Laurent Capelle
(10)
,
John de Groot
(3)
,
Francesco Dimeco
(11, 12)
,
François Ducray
(13, 14)
,
Walid Farah
(15)
,
Gaetano Finocchiaro
(11)
,
Stéphane Goutagny
(16)
,
Carlos Kamiya-Matsuoka
(3)
,
Cinzia Lavarino
,
Hugues Loiseau
(17)
,
Véronique Lorgis
(18)
,
Carlo E Marras
,
Ian Mccutcheon
(3)
,
Do-Hyun Nam
(19)
,
Susanna Ronchi
(6, 7, 8)
,
Veronica Saletti
(11)
,
Romuald Seizeur
(20)
,
John Slopis
(3)
,
Mariona Suñol
,
Fanny Vandenbos
(21)
,
Pascale Varlet
(22, 23)
,
Dominique Vidaud
(24, 25)
,
Colin Watts
(26)
,
Viviane Tabar
(27)
,
David E. Reuss
(28, 29)
,
Seung-Ki Kim
,
David Meyronet
(13)
,
Karima Mokhtari
(6, 7, 8)
,
Hector Salvador
,
Krishna P Bhat
(3)
,
Marica Eoli
(11)
,
Marc Sanson
(6, 7, 8)
,
Anna Lasorella
(1)
,
Antonio Iavarone
(1)
1
CUMC -
Columbia University Medical Center
2 University of Sannio [Benevento]
3 The University of Texas M.D. Anderson Cancer Center [Houston]
4 CHU Montpellier
5 Hôpital Gui de Chauliac [CHU Montpellier]
6 ICM - Institut du Cerveau = Paris Brain Institute
7 SU FM - Sorbonne Université - Faculté de Médecine
8 SU - Sorbonne Université
9 MUSC - Medical University of South Carolina [Charleston]
10 CHU Pitié-Salpêtrière [AP-HP]
11 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
12 UNIMI - Università degli Studi di Milano = University of Milan
13 HCL - Hospices Civils de Lyon
14 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
15 Service de neurochirurgie [CHU Dijon]
16 Hôpital Beaujon [AP-HP]
17 CHU Bordeaux
18 Département d'oncologie médicale [Centre Georges-François Leclerc]
19 SKKU - Sungkyunkwan University [Suwon]
20 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
21 CHU - Hôpital Pasteur [Nice]
22 U894 - Centre de Psychiatrie et Neurosciences
23 Centre Hospitalier Sainte Anne [Paris]
24 EA 7331 - Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux
25 Hôpital Cochin [AP-HP]
26 University of Birmingham [Birmingham]
27 Memorial Sloane Kettering Cancer Center [New York]
28 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
29 Universität Heidelberg [Heidelberg] = Heidelberg University
2 University of Sannio [Benevento]
3 The University of Texas M.D. Anderson Cancer Center [Houston]
4 CHU Montpellier
5 Hôpital Gui de Chauliac [CHU Montpellier]
6 ICM - Institut du Cerveau = Paris Brain Institute
7 SU FM - Sorbonne Université - Faculté de Médecine
8 SU - Sorbonne Université
9 MUSC - Medical University of South Carolina [Charleston]
10 CHU Pitié-Salpêtrière [AP-HP]
11 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
12 UNIMI - Università degli Studi di Milano = University of Milan
13 HCL - Hospices Civils de Lyon
14 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
15 Service de neurochirurgie [CHU Dijon]
16 Hôpital Beaujon [AP-HP]
17 CHU Bordeaux
18 Département d'oncologie médicale [Centre Georges-François Leclerc]
19 SKKU - Sungkyunkwan University [Suwon]
20 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
21 CHU - Hôpital Pasteur [Nice]
22 U894 - Centre de Psychiatrie et Neurosciences
23 Centre Hospitalier Sainte Anne [Paris]
24 EA 7331 - Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux
25 Hôpital Cochin [AP-HP]
26 University of Birmingham [Birmingham]
27 Memorial Sloane Kettering Cancer Center [New York]
28 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
29 Universität Heidelberg [Heidelberg] = Heidelberg University
Luc Bauchet
- Fonction : Auteur
- PersonId : 760714
- ORCID : 0000-0003-1077-2496
Mario Cangiano
- Fonction : Auteur
François Ducray
- Fonction : Auteur
- PersonId : 919913
Stéphane Goutagny
- Fonction : Auteur
- PersonId : 740516
- IdHAL : stephanegoutagny
- ORCID : 0000-0001-6975-9945
Cinzia Lavarino
- Fonction : Auteur
Carlo E Marras
- Fonction : Auteur
Romuald Seizeur
- Fonction : Auteur
- PersonId : 903989
Mariona Suñol
- Fonction : Auteur
Pascale Varlet
- Fonction : Auteur
- PersonId : 762020
- ORCID : 0000-0002-8164-1517
Seung-Ki Kim
- Fonction : Auteur
David Meyronet
- Fonction : Auteur
- PersonId : 774596
- ORCID : 0000-0001-9943-4578
Karima Mokhtari
- Fonction : Auteur
- PersonId : 942862
Hector Salvador
- Fonction : Auteur
Marc Sanson
- Fonction : Auteur
- PersonId : 760119
- ORCID : 0000-0002-1813-8476
Résumé
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.
Domaines
Sciences du Vivant [q-bio]
Fichier principal
The molecular landscape of glioma in patients with Neurofibromatosis 1_sans marque.pdf (8.65 Mo)
Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...