Format

Send to

Choose Destination
Neuro Oncol. 2018 Jul 5;20(8):1092-1100. doi: 10.1093/neuonc/noy019.

Identification of novel recurrent ETV6-IgH fusions in primary central nervous system lymphoma.

Author information

1
Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne Universités, UPMC, University Paris, Institut du Cerveau et de la Moelle épinière, INSERM, CNRS UMR, Paris, France.
2
Institut du Cerveau et de la Moelle épinière, Plateforme iGenSeq, Paris, France.
3
Département de pathologie cellulaire et tissulaire, CHU d'Angers, Angers, France.
4
Neuropathologie, CHRU Nancy, Nancy, France.
5
Onconeurotek, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
6
Genosplice, Institut du Cerveau et de la Moelle épinière, Paris, France.
7
Institut du Cerveau et de la Moelle épinière, ICONICS (bioinformatic and biostatistics core facility), Paris, France.
8
Neuropathologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
9
Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Service d'Anatomie et Cytologie Pathologiques, Paris, France.
10
Centre Hospitalier Universitaire Bicêtre, Assistance Publique-Hôpitaux de Paris, Service d'anatomopathologie, Le Kremlin-Bicêtre Cedex, France.
11
Hospices Civils de Lyon, Hôpital Neurologique, Bron, France and INSERM U842, Université Lyon, Lyon, France.
12
Centre Hospitalier Universitaire La Timone, Laboratoire d'anatomie pathologique-neuropathologique and Tumorothèque de l'Assistance Publique-Hôpitaux de Marseille (AC 2013-1786), Marseille Cedex, France.
13
Aix-Marseille University, AP-HM, CNRS, INP, Institute Neurophypathology, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France.
14
Hôpital Foch, Service d'anatomie pathologique, Suresnes, France.
15
Centre hospitalier Sainte Anne, Université Paris Descartes, Paris, France.
16
Centre Hospitalier Universitaire Bordeaux, Service de Pathologie, Site Pellegrin,Rue Léo Saignat Victor Segalen University, Bordeaux Cedex, France.
17
Hématologie, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France; and UMR_S, Sorbonne Universités, UPMC, University Paris, Paris, France.
18
Service de Neurologie Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
19
Réseau Expert National LOC (Lymphomes Oculo-Cérébraux).
20
Hôpital René Huguenin, Institut Curie, Service d'Hématologie, Saint Cloud, France.

Abstract

Background:

Primary central nervous system lymphoma (PCNSL) represents a particular entity within non-Hodgkin lymphomas and is associated with poor outcome. The present study addresses the potential clinical relevance of chimeric transcripts in PCNSL discovered by using RNA sequencing (RNA-seq).

Methods:

Seventy-two immunocompetent and newly diagnosed PCNSL cases were included in the present study. Among them, 6 were analyzed by RNA-seq to detect new potential fusion transcripts. We confirmed the results in the remaining 66 PCNSL. The gene fusion was validated by fluorescence in situ hybridization (FISH) using formalin-fixed paraffin-embedded (FFPE) samples. We assessed the biological and clinical impact of one new gene fusion.

Results:

We identified a novel recurrent gene fusion, E26 transformation-specific translocation variant 6-immunoglobulin heavy chain (ETV6-IgH). Overall, ETV6-IgH was found in 13 out of 72 PCNSL (18%). No fusion conserved an intact functional domain of ETV6, and ETV6 was significantly underexpressed at gene level, suggesting an ETV6 haploinsufficiency mechanism. The presence of the gene fusion was also validated by FISH in FFPE samples. Finally, PCNSL samples harboring ETV6-IgH showed a better prognosis in multivariate analysis, P = 0.03, hazard ratio = 0.33, 95% CI = 0.12-0.88. The overall survival at 5 years was 69% for PCNSL harboring ETV6-IgH versus 29% for samples without this gene fusion.

Conclusions:

ETV6-IgH is a new potential surrogate marker of PCNSL with favorable prognosis with ETV6 haploinsufficiency as a possible mechanism. The potential clinical impact of ETV6-IgH should be validated in larger prospective studies.

PMID:
29432597
PMCID:
PMC6280140
[Available on 2019-07-05]
DOI:
10.1093/neuonc/noy019

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center