Oncotarget

Research Papers:

Relapsed diffuse large B-cell lymphoma present different genomic profiles between early and late relapses

Julien Broséus, Gaili Chen, Sébastien Hergalant, Gérard Ramstein, Nicolas Mounier, Jean-Louis Guéant, Pierre Feugier, Christian Gisselbrecht, Catherine Thieblemont and Rémi Houlgatte _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:83987-84002. https://doi.org/10.18632/oncotarget.9793

Metrics: PDF 2541 views  |   HTML 1823 views  |   ?  


Abstract

Julien Broséus1,2, Gaili Chen3,*, Sébastien Hergalant1,*, Gérard Ramstein4, Nicolas Mounier5, Jean-Louis Guéant1,6, Pierre Feugier1,7, Christian Gisselbrecht8, Catherine Thieblemont8,9,** and Rémi Houlgatte1,10,**

1 Inserm U954, Faculty of Medicine, Nancy, France

2 Hematology, Laboratory Department, University Hospital of Nancy, Nancy, France

3 ZhongNan Hospital of Wuhan University, Wuhan, China

4 LINA DUKe, UMR 6241, Université de Nantes, Nantes, France

5 Hemato-oncology, University Hospital of l’Archet, Nice, France

6 Biochemistry, Laboratory Department, University Hospital of Nancy, Nancy, France

7 Hematology Department, University Hospital of Nancy, Nancy, France

8 APHP, Saint-Louis Hospital, Hemato-Oncology Department, Paris, France

9 Paris Diderot University-Sorbonne Paris-Cité, Paris, France

10 DRCI, University Hospital of Nancy, Nancy, France

* These authors contributed equally to this work

** Last authors equally contributed to this work

Correspondence to:

Rémi Houlgatte, email:

Catherine Thieblemont, email:

Keywords: diffuse large B-cell lymphoma, early relapse, late relapse, genomics, copy number variations

Received: April 18, 2016 Accepted: May 13, 2016 Published: June 02, 2016

Abstract

Despite major advances in first-line treatment, a significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) will experience treatment failure. Prognosis is particularly poor for relapses occurring less than one year after the end of first-line treatment (early relapses/ER) compared to those occurring more than one year after (late relapses/LR). To better understand genomic alterations underlying the delay of relapse, we identified copy number variations (CNVs) on 39 tumor samples from a homogeneous series of patients included in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) prospective study. To identify CNVs associated with ER or LR, we devised an original method based on Significance Analysis of Microarrays, a permutation-based method which allows control of false positives due to multiple testing. Deletions of CDKN2A/B (28%) and IBTK (23%) were frequent events in relapsed DLBCLs. We identified 56 protein-coding genes and 25 long non-coding RNAs with significantly differential CNVs distribution between ER and LR DLBCLs, with a false discovery rate < 0.05. In ER DLBCLs, CNVs were related to transcription regulation, cell cycle and apoptosis, with duplications of histone H1T (31%), deletions of DIABLO (26%), PTMS (21%) and CK2B (15%). In LR DLBCLs, CNVs were related to immune response, with deletions of B2M (20%) and CD58 (10%), cell proliferation regulation, with duplications of HES1 (25%) and DVL3 (20%), and transcription regulation, with MTERF4 deletions (20%). This study provides new insights into the genetic aberrations in relapsed DLBCLs and suggest pathway-targeted therapies in ER and LR DLBCLs.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 9793