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© Research
Publication : Neuro-oncology

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Neuro-oncology - 08 Feb 2018

Bruno A, Labreche K, Daniau M, Boisselier B, Gauchotte G, Royer-Perron L, Rahimian A, Lemoine F, de la Grange P, Guégan J, Bielle F, Polivka M, Adam C, Meyronet D, Figarella-Branger D, Villa C, Chrétien F, Eimer S, Davi F, Rousseau A, Houillier C, Soussain C, Mokhtari K, Hoang-Xuan K, Alentorn A

Link to Pubmed [PMID] – 29432597

Neuro-oncology 2018 Feb;

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 PCSNL discovered by using RNA-sequencing (RNA-Seq).

Methods: Seventy-two immunocompetent and newly diagnosed PCNSL cases were included in the present study. Among them, six 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 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-value=0.03, HR=0.33, 95% interval confidence (IC95) [0.12-0.88]. The overall survival at 5 years was of 69% for PCNSL harboring ETV6-IgH vs 29% for samples without this gene fusion.

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

https://www.ncbi.nlm.nih.gov/pubmed/29432597