Format

Send to

Choose Destination
Neuro Oncol. 2019 May 17. pii: noz088. doi: 10.1093/neuonc/noz088. [Epub ahead of print]

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

Author information

1
Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey; UK.
2
Inserm, U 1127, ICM, F-75013 Paris, France; CNRS, UMR 7225, ICM, Paris, France; Institut du Cerveau et de la Moelle épinière ICM, Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, Paris, France.
3
Institut du Cerveau et de la Moelle épinière, Plateforme iGenSeq, 47 Boulevard de.
4
AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Paris, France. Universités, UPMC Université Paris 06, UMR S 1127, Paris, France.
5
Department of Neurology, Hôpitaux Civils de Colmar, 68024, Colmar Cedex, France.
6
Department of Medical Oncology, Institut Bergnoié, Bordeaux, France.
7
U1218 INSERM Research Unit, Bordeaux, France.
8
Neuro-oncology Department, Nancy University Hospital and CRAN UMR 7039 CNRS, SBS BEAM Department, Nancy University, Vandoeuvre-lès-Nancy, France.
9
Department of pathology and Neuropathology, Hôpital de la Timone, Aix-Marseille Univ, AP-HM, Marseille, France.
10
AMU, CRO2, Marseille, France.
11
Department of Hematology, Dijon University Hospital, Dijon, Dijon, France.
12
Department of Hematology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
13
Department of Hematology, Cancer Center Henri Henri Becquerel Center, Rouen, France and INSERM U1245, Cancer Center Henri Becquerel, Institute of Research and Innovation in Biomedicine, University of Normandy, Rouen, France.
14
Department of Hematology, IUCT - Oncopole, Toulouse - France.
15
Institut du Cancer Val d'Aurelle 34298 Montpellier Cedex 5 - France.
16
Department of Hematology, University Hospital of Caen, Caen, France.
17
Department of Hematology, CHRU Besançon, Besançon, France.
18
AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Neuropathology Raymond Escourolle, Paris, France.
19
OncoNeuroTek, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
20
Neurospin Centre CEA, Saclay, Gif sur Yvette, France.
21
Department of Hematology, Hôpital René Huguenin, Institut Curie, Saint-Cloud, France.

Abstract

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 two new genome-wide association studies of PCNSL totaling 475 cases and 1,134 controls of European ancestry. To increase genomic resolution, we imputed >10 million single-nucleotide polymorphisms (SNPs) 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 patterns by capture Hi-C data.

RESULTS:

We identified independent risk loci at 3p22.1 (rs41289586, ANO10, P = 2.17 x 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 non-coding 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.

PMID:
31102405
PMCID:
PMC6682213
[Available on 2020-08-01]
DOI:
10.1093/neuonc/noz088

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center