期刊
NEURO-ONCOLOGY
卷 20, 期 8, 页码 1092-1100出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/noy019
关键词
ETV6-IgH; fusion gene; haploinsufficiency; primary CNS lymphoma; RNA sequencing
资金
- Ligue nationale contre le cancer
- Institut National du Cancer
- Association pour la recherche sur les tumeurs cerebrales (ARTC)
- Canceropole Ile-de-France Emergence [2015-1-EMERG-05-INSERM6-1]
- Ligue nationale contre le cancer (Comite du Val d'Oise) [R14044DD]
- Ligue Nationale contre le cancer Recherche epidemiologique [PRE2015.LNCC]
- Fondation pour la Recherche Medicale [FDT20140930968]
- program Investissements d'avenir [ANR-10-IAIHU-06]
- Institut National du Cancer (INCa) (Reseau Expert National LOC, Lymphomes Oculo-Cerebraux)
- Lymphomes Oculo-Cerebraux (LOC) study group network (Reseau national de centres experts des lymphomes primitifs du systeme nerveux central)
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据