Contributions
Abstract: EP853
Type: E-Poster Presentation
Session title: Lymphoma Biology & Translational Research
Background
The current World Health Organization (WHO) classification outlines the Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) as a distinct entity while its comprehensive genomic characterization remains fragmentary.
Aims
The substantial aim of the present study was to compile an extensive genomic landscape of EBV+ DLBCL (NOS).
Methods
In the current study, the genomic landscape of 47 cases of this rare entity has been characterized by whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS) and fluorescence in-situ hybridization (FISH).
Results
Genomic data from WGS detected an accumulation of mutations with impact on WNT signalling (FRAT1, SFRP5), the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL-6/JAK/STAT (SOCS1/3, STAT3) and alterations affecting immunological response like interferon-related signalling. Moreover, upon WGS-analysis there were several structural aberrations including 6q-deletions in 5/8 cases which underwent subsequent validation by FISH (14/32 cases). Present data reveal a distinctive genomic profile from EBV-negative DLBCL. Frequent typical DLBCL mutations could be identified in ARID1A (45%), KMT2A/D (32/30%), ANKRD11 (32%), NOTCH2 (32%) as well as EBV+ DLBCL (NOS) exclusive mutations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%) and YY1 (6%).
Conclusion
We delineate the mutational landscape of EBV+ DLBCL (NOS) and comprehensively explore its pathobiological origin detecting several exclusive oncogenic drivers distinctive from other aggressive B-cell lymphoma subtypes. Moreover, we find deletions on chromosome 6 to be a highly recurrent cytogenetic feature of this rare entity. Current genomic findings contribute to the particular specification of the molecular taxonomy for aggressive B-cell lymphomas harbouring the potential to guide future treatment strategies.
Keyword(s): B cell lymphoma, Diffuse large B cell lymphoma, EBV, Genomics
Abstract: EP853
Type: E-Poster Presentation
Session title: Lymphoma Biology & Translational Research
Background
The current World Health Organization (WHO) classification outlines the Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) as a distinct entity while its comprehensive genomic characterization remains fragmentary.
Aims
The substantial aim of the present study was to compile an extensive genomic landscape of EBV+ DLBCL (NOS).
Methods
In the current study, the genomic landscape of 47 cases of this rare entity has been characterized by whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS) and fluorescence in-situ hybridization (FISH).
Results
Genomic data from WGS detected an accumulation of mutations with impact on WNT signalling (FRAT1, SFRP5), the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL-6/JAK/STAT (SOCS1/3, STAT3) and alterations affecting immunological response like interferon-related signalling. Moreover, upon WGS-analysis there were several structural aberrations including 6q-deletions in 5/8 cases which underwent subsequent validation by FISH (14/32 cases). Present data reveal a distinctive genomic profile from EBV-negative DLBCL. Frequent typical DLBCL mutations could be identified in ARID1A (45%), KMT2A/D (32/30%), ANKRD11 (32%), NOTCH2 (32%) as well as EBV+ DLBCL (NOS) exclusive mutations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%) and YY1 (6%).
Conclusion
We delineate the mutational landscape of EBV+ DLBCL (NOS) and comprehensively explore its pathobiological origin detecting several exclusive oncogenic drivers distinctive from other aggressive B-cell lymphoma subtypes. Moreover, we find deletions on chromosome 6 to be a highly recurrent cytogenetic feature of this rare entity. Current genomic findings contribute to the particular specification of the molecular taxonomy for aggressive B-cell lymphomas harbouring the potential to guide future treatment strategies.
Keyword(s): B cell lymphoma, Diffuse large B cell lymphoma, EBV, Genomics