Genomics

Dataset Information

39

Relapsed diffuse large B-cell lymphoma present different genomic patterns of alterations between early and late relapses


ABSTRACT: Despite major advances in first-line treatment, a significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) will experience treatment failure. Time of relapse is a major prognostic parameter in this context, with a particularly poor prognosis for early relapse. Our purpose was to determine genomic alterations associated with early-relapsed (ER) and late-relapsed (LR) DLBCLs, using high resolution array-based comparative genomic hybridization and integrating structural abnormalities and gene expression of 39 samples from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) study. ER and LR DLBCLs present a similar landscape of large copy number variations (CNVs), with an average 14.89 and 16.11 CNVs per sample, respectively (p=0.81). 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, genetic abnormalities were related to regulation of transcription, cell cycle and apoptosis, with duplications of histone H1T (31%), deletions of DIABLO (26%), PTMS (21%) and CK2B (15%). In LR DLBCLs, genetic aberrations were related to immune response, with alterations of IgHV (40%), IgKV (15%), and deletions of B2M (20%) and CD58 (10%), regulation of cell proliferation, with duplications of HES1 and DVL3 (25% and 20%, respectively) and regulation of transcription, with MTERF4 deletions (20%). This study provides new insights into the genetic abnormalities in relapsed DLBCLs. Dysregulation of cell cycle, apoptosis and gene transcription may indicate targeted therapy. Overall design: Comparative study of CNVs in 19 early- and 20 late-relapsed DLBCLs

INSTRUMENT(S): [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array

SUBMITTER: Sebastien Hergalant 

PROVIDER: GSE73791 | GEO | 2016-09-26

SECONDARY ACCESSION(S): PRJNA297892

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
GSE73791_Chromosome_1.txt.gz Txt
GSE73791_Chromosome_10.txt.gz Txt
GSE73791_Chromosome_11.txt.gz Txt
GSE73791_Chromosome_12.txt.gz Txt
GSE73791_Chromosome_13.txt.gz Txt
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Publications

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

Broséus Julien J   Chen Gaili G   Hergalant Sébastien S   Ramstein Gérard G   Mounier Nicolas N   Guéant Jean-Louis JL   Feugier Pierre P   Gisselbrecht Christian C   Thieblemont Catherine C   Houlgatte Rémi R  

Oncotarget 20161201 51


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 sam  ...[more]

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