A genome-wide association study identifies susceptibility loci for primary central nervous system lymphoma at 6p25.3 and 3p22.1: a LOC Network study.

Central Nervous System Central Nervous System Neoplasms / genetics Genome-Wide Association Study Humans Lymphoma, Large B-Cell, Diffuse / genetics Lymphoma, Non-Hodgkin
GWAS cancer susceptibility primary CNS lymphoma

Journal

Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420

Informations de publication

Date de publication:
05 08 2019
Historique:
pubmed: 19 5 2019
medline: 28 4 2021
entrez: 19 5 2019
Statut: ppublish

Résumé

Primary central nervous system lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin lymphoma. PCNSL is a distinct subtype of non-Hodgkin lymphoma, with over 95% of tumors belonging to the diffuse large B-cell lymphoma (DLBCL) group. We have conducted a genome-wide association study (GWAS) on immunocompetent patients to address the possibility that common genetic variants influence the risk of developing PCNSL. We performed a meta-analysis of 2 new GWASs of PCNSL totaling 475 cases and 1134 controls of European ancestry. To increase genomic resolution, we imputed >10 million single nucleotide polymorphisms using the 1000 Genomes Project combined with UK10K as reference. In addition we performed a transcription factor binding disruption analysis and investigated the patterns of local chromatin by Capture Hi-C data. We identified independent risk loci at 3p22.1 (rs41289586, ANO10, P = 2.17 × 10-8) and 6p25.3 near EXOC2 (rs116446171, P = 1.95 x 10-13). In contrast, the lack of an association between rs41289586 and DLBCL suggests distinct germline predisposition to PCNSL and DLBCL. We found looping chromatin interactions between noncoding regions at 6p25.3 (rs11646171) with the IRF4 promoter and at 8q24.21 (rs13254990) with the MYC promoter, both genes with strong relevance to B-cell tumorigenesis. To our knowledge this is the first study providing insight into the genetic predisposition to PCNSL. Our findings represent an important step in defining the contribution of common genetic variation to the risk of developing PCNSL.

Sections du résumé

BACKGROUND
Primary central nervous system lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin lymphoma. PCNSL is a distinct subtype of non-Hodgkin lymphoma, with over 95% of tumors belonging to the diffuse large B-cell lymphoma (DLBCL) group. We have conducted a genome-wide association study (GWAS) on immunocompetent patients to address the possibility that common genetic variants influence the risk of developing PCNSL.
METHODS
We performed a meta-analysis of 2 new GWASs of PCNSL totaling 475 cases and 1134 controls of European ancestry. To increase genomic resolution, we imputed >10 million single nucleotide polymorphisms using the 1000 Genomes Project combined with UK10K as reference. In addition we performed a transcription factor binding disruption analysis and investigated the patterns of local chromatin by Capture Hi-C data.
RESULTS
We identified independent risk loci at 3p22.1 (rs41289586, ANO10, P = 2.17 × 10-8) and 6p25.3 near EXOC2 (rs116446171, P = 1.95 x 10-13). In contrast, the lack of an association between rs41289586 and DLBCL suggests distinct germline predisposition to PCNSL and DLBCL. We found looping chromatin interactions between noncoding regions at 6p25.3 (rs11646171) with the IRF4 promoter and at 8q24.21 (rs13254990) with the MYC promoter, both genes with strong relevance to B-cell tumorigenesis.
CONCLUSION
To our knowledge this is the first study providing insight into the genetic predisposition to PCNSL. Our findings represent an important step in defining the contribution of common genetic variation to the risk of developing PCNSL.

Identifiants

DOI: 10.1093/neuonc/noz088 PMID: 31102405 PMC: PMC6682213
pubmed: 31102405
pii: 5491436
doi: 10.1093/neuonc/noz088
pmc: PMC6682213
doi:

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1039-1048

Investigateurs

Marie-Pierre Moles-Moreau (MP)
Rémy Gressin (R)
Vincent Delwail (V)
Franck Morschhauser (F)
Philippe Agapé (P)
Arnaud Jaccard (A)
Hervé Ghesquieres (H)
Adrian Tempescul (A)
Emmanuel Gyan (E)
Jean-Pierre Marolleau (JP)
Roch Houot (R)
Luc Fornecker (L)
Anna-Luisa Di Stefano (AD)
Inès Detrait (I)
Amithys Rahimian (A)
Mark Lathrop (M)
Diane Genet (D)
Frédéric Davi (F)
Nathalie Cassoux (N)
Valérie Touitou (V)
Sylvain Choquet (S)
Anne Vital (A)
Marc Polivka (M)
Dominique Figarella-Branger (D)
Alexandra Benouaich-Amiel (A)
Chantal Campello (C)
Frédéric Charlotte (F)
Nadine Martin-Duverneuil (N)
Loïc Feuvret (L)
Aurélie Kas (A)
Soledad Navarro (S)
Chiara Villa (C)
Franck Bielle (F)
Fabrice Chretien (F)
Marie Christine Tortel (MC)
Guillaume Gauchotte (G)
Emmanuelle Uro-Coste (E)
Catherine Godfrain (C)
Valérie Rigau (V)
Myrto Costopoulos (M)
Magalie Le Garff-Tavernier (ML)
David Meyronnet (D)
Audrey Rousseau (A)
Clovis Adam (C)
Thierry Lamy (T)
Cécile Chabrot (C)
Eileen M Boyle (EM)
Marie Blonski (M)
Anna Schmitt (A)

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Karim Labreche (K)

Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.
(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.

Mailys Daniau (M)

(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.
ICM, iGenSeq Platform, Paris, France.

Amit Sud (A)

Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.

Philip J Law (PJ)

Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.

Louis Royer-Perron (L)

(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.
Neurology Service 2 (Mazarin), Public Assistance-Hospitals of Paris, Hospital Group of Pitié-Salpêtrière, Paris, France; Pierre and Marie Curie University, Paris 6, Paris, France.

Amy Holroyd (A)

Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.

Peter Broderick (P)

Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.

Molly Went (M)

Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.

Marion Benazra (M)

(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.
ICM, iGenSeq Platform, Paris, France.

Guido Ahle (G)

Department of Neurology, Colmar Civil Hospitals, Colmar Cedex, France.

Pierre Soubeyran (P)

Department of Medical Oncology, Bergnoié Institute, Bordeaux, France.
Inserm Research Unit U1218, Bordeaux, France.

Luc Taillandier (L)

Neuro-oncology Department, Nancy University Hospital and The Center of Research in Automatic Control of Nancy, Joint Research Unit 7039, National Center for Scientific Research, SBS BEAM Department, Nancy University, Vandoeuvre-lès-Nancy, France.

Olivier L Chinot (OL)

Department of Pathology and Neuropathology, Timone Hospital, Aix-Marseille University (AMU), Public Assistance-Hospitals of Marseille, Marseille, France.
AMU Research Center in Oncology Biology and Oncopharmacology, Marseille, France.

Olivier Casasnovas (O)

Department of Hematology, Dijon University Hospital, Dijon, France.

Jacques-Olivier Bay (JO)

Department of Hematology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

Fabrice Jardin (F)

Department of Hematology, Henri Becquerel Cancer Center, Rouen, France and Inserm U1245, Henri Becquerel Cancer Center, Institute of Research and Innovation in Biomedicine, University of Normandy, Rouen, France.

Lucie Oberic (L)

Department of Hematology, University Cancer Institute of Toulouse-Oncopole, Toulouse, France.

Michel Fabbro (M)

Val d'Aurelle Cancer Institute, Montpellier, France.

Gandhi Damaj (G)

Department of Hematology, University Hospital of Caen, Caen, France.

Annie Brion (A)

Department of Hematology, Regional and University Hospitals Besançon, Besançon, France.

Karima Mokhtari (K)

(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.
Raymond Escourolle Department of Neuropathology, Public Assistance-Hospitals of Paris, Hospital Group of Pitié-Salpêtrière, Paris, France.
OncoNeuroTek, ICM, Paris, France.

Cathy Philippe (C)

Neurospin Centre CEA, Gif sur Yvette, France.

Marc Sanson (M)

(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.
Neurology Service 2 (Mazarin), Public Assistance-Hospitals of Paris, Hospital Group of Pitié-Salpêtrière, Paris, France; Pierre and Marie Curie University, Paris 6, Paris, France.
OncoNeuroTek, ICM, Paris, France.

Caroline Houillier (C)

(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.

Carole Soussain (C)

Department of Hematology, René Huguenin Hospital, Curie Institute, Saint-Cloud, France.

Khê Hoang-Xuan (K)

(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.
Neurology Service 2 (Mazarin), Public Assistance-Hospitals of Paris, Hospital Group of Pitié-Salpêtrière, Paris, France; Pierre and Marie Curie University, Paris 6, Paris, France.

Richard S Houlston (RS)

Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.

Agusti Alentorn (A)

(i) National Institute of Health and Medical Research (Inserm) U 1127, Paris, France, (ii) National Center for Scientific Research, Joint Research Unit 7225, Paris, France, (iii) Brain and Spine Institute (ICM), Paris, France, and (iv) Sorbonne University, Pierre and Marie Curie University, Paris 6, Paris, France.
Neurology Service 2 (Mazarin), Public Assistance-Hospitals of Paris, Hospital Group of Pitié-Salpêtrière, Paris, France; Pierre and Marie Curie University, Paris 6, Paris, France.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Système nerveux › Système nerveux central › A genome-wide association study identifies...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › A genome-wide association study identifies...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › A genome-wide association study identifies...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A genome-wide association study identifies...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Lymphome malin non hodgkinien › Lymphome B › Lymphome B diffus à grandes cellules › A genome-wide association study identifies...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Lymphome malin non hodgkinien › A genome-wide association study identifies...