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Journal articles
Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease
J.-F. Emile
1, 2
E. Diamond
3
Z. Helias-Rodzewicz
2, 1
F. Cohen-Aubart
4, 5
F. Charlotte
6
D. Hyman
7
E. Kim
8
R. Rampal
8
M. Patel
8
C. Ganzel
9
S. Aumann
8
G. Faucher
2, 1
C. Le Gall
2, 1
K. Leroy
10
M. Colombat
11
J.-E. Kahn
12
S. Trad
13
P. Nizard
2, 14, 15
J. Donadieu
2
V. Taly
14, 15, *
Zahir Amoura
16
O. Abdel-Wahab
8
J. Haroche
17, 5
*
Corresponding author
J.-F. Emile 1, 2
Author
E. Diamond 3
Author
Z. Helias-Rodzewicz 2, 1
Author
F. Cohen-Aubart 4, 5
Author
S. Trad 13
Author
P. Nizard 2, 14, 15
Author
J. Donadieu 2
Author
V. Taly 14, 15
Correspondent author IdHAL : valerie-taly
Zahir Amoura 16
Author Employer institution : CHU Pitié-Salpêtrière [AP-HP]
O. Abdel-Wahab 8
Author
J. Haroche 17, 5
Author
1
Service d'anatomie pathologique [CHU Ambroise-Paré] (92100 Boulogne - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôpital Ambroise Paré [AP-HP] (9, avenue Charles de Gaulle92104 Boulogne-Billancourt cedex - France)
2
BECCOH - Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (Hôpital Ambroise Paré, 9 avenue Charles de Gaulle
92104 Boulogne - France)
- UVSQ - Université de Versailles Saint-Quentin-en-Yvelines : UR 4340 (55 avenue de Paris - 78035 Versailles cedex - France)
- Université Paris-Saclay (Espace Technologique, Bat. Discovery - RD 128 - 2e ét., 91190 Saint-Aubin - France)
3
Department of Neurology [New York, NY, USA] (United States)
- Columbia University [New York] (Columbia University in the City of New York 2960 Broadway New York, NY 10027-6902 - United States)
4
Service de médecine interne [CHU Pitié-Salpétrière] (47-83, boulevard de l'Hôpital 75651 PARIS Cedex 13 - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
5
Centre de référence français pour les maladies auto-immunes et systémiques rares [Hôpital Pitié-Salpêtrière - APHP] (France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
6
Service d’anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (83 Bd de l’hôpital, F-75013 Paris - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
7
Experimental Therapeutics Unit [New York, NY, USA] (United States)
- Memorial Sloane Kettering Cancer Center [New York] (1275 York Avenue New York, NY 10065 - United States)
8
Human Oncology and Pathogenesis Program and Leukemia Service [New York, NY, USA] (United States)
- Memorial Sloane Kettering Cancer Center [New York] (1275 York Avenue New York, NY 10065 - United States)
- Weill Medical College of Cornell University [New York] (Manhattan - United States)
9
Department of Hematology [Jerusalem, Israel] (Israel)
10
Département de pathologie [Mondor] (51 Av Maréchal de Lattre de Tassigny, 94000 Créteil - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôpital Henri Mondor (France)
- UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (61 avenue du Général de Gaulle - 94010 Créteil cedex - France)
11
Service de Pathologie [Hôpital Foch] (Suresnes - France)
- Hôpital Foch [Suresnes] (40 Rue Worth 92150 Suresnes - France)
12
Service de Médecine Interne [Hôpital Fosh, Suresnes] (France)
- Hôpital Foch [Suresnes] (40 Rue Worth 92150 Suresnes - France)
13
Service de Médecine Interne [AP-HP Hôpital Ambroise Paré] (France)
- Hôpital Ambroise Paré [AP-HP] (9, avenue Charles de Gaulle92104 Boulogne-Billancourt cedex - France)
14
MEPPOT - U1147 - Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (Centre Universitaire des Saints Pères - 45 rue des Saints Pères 75006 Paris - France)
- UPD5 - Université Paris Descartes - Paris 5 : UMR_S 1147 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1147 (101, rue de Tolbiac, 75013 Paris - France)
15
SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
16
Institut E3M [CHU Pitié-Salpêtrière] (France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
17
Service de Médecine Interne [CHU HEGP] (20, rue Leblanc 75015 Paris - France)
- Centre de référence des syndromes drépanocytaires majeurs (France)
- HEGP - Hôpital Européen Georges Pompidou [APHP] (20, rue Leblanc, 75015 Paris - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
Abstract : Erdheim-Chester disease (ECD) is a rare histiocytic disorder that is challenging to diagnose and treat. We performed molecular analysis of BRAF in the largest cohort of ECD patients studied to date followed by N/KRAS, PIK3CA, and AKT1 mutational analysis in BRAF wild-type patients. Forty-six of 80 (57.5%) of patients were BRAFV600E-mutant. NRAS mutations were detected in 3 of 17 ECD BRAFV600E wild-type patients. PIK3CA mutations (p.E542K, p.E545K, p.A1046T, and p.H1047R) were detected in 7 of 55 patients, 4 of whom also had BRAF mutations. Mutant NRAS was present in peripheral blood CD14(+) cells, but not lymphoid cells, from an NRASQ61R mutant patient. Our results underscore the central role of RAS-RAF-MEK-ERK activation in ECD and identify an important role of activation of RAS-PI3K-AKT signaling in ECD. These results provide a rationale for targeting mutant RAS or PI3K/AKT/mTOR signaling in the subset of ECD patients with NRAS or PIK3CA mutations.
Document type :
Journal articles
Complete list of metadatas
https://www.hal.inserm.fr/inserm-02299579
Contributor : Valerie Taly <>
Submitted on : Friday, September 27, 2019 - 6:28:15 PM
Last modification on : Tuesday, November 17, 2020 - 1:58:03 PM
Long-term archiving on: : Monday, February 10, 2020 - 5:36:20 AM
Contributor : Valerie Taly <>
Submitted on : Friday, September 27, 2019 - 6:28:15 PM
Last modification on : Tuesday, November 17, 2020 - 1:58:03 PM
Long-term archiving on: : Monday, February 10, 2020 - 5:36:20 AM
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Identifiers
- HAL Id : inserm-02299579, version 1
- DOI : 10.1182/blood-2014-04-570937
- PUBMED : 25150293
- PUBMEDCENTRAL : PMC4224196
Collections
UPEC-UPEM | UVSQ | UPMC | UNIV-PARIS5 | USPC | SORBONNE-UNIVERSITE | UPEC | UNIV-PARIS | BCOH
Citation
J.-F. Emile, E. Diamond, Z. Helias-Rodzewicz, F. Cohen-Aubart, F. Charlotte, et al.. Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease. Blood, American Society of Hematology, 2014, 124 (19), pp.3016-3019. ⟨10.1182/blood-2014-04-570937⟩. ⟨inserm-02299579⟩
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