TY - JOUR
T1 - Prevalence of targetable oncogenic mutations and genomic alterations in Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly
AU - Gebauer, Niklas
AU - Gebauer, Judith
AU - Hardel, Tim Tristan
AU - Bernard, Veronica
AU - Biersack, Harald
AU - Lehnert, Hendrik
AU - Rades, Dirk
AU - Feller, Alfred Christian
AU - Thorns, Christoph
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Abstract Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma (DLBCL) of the elderly constitutes a provisional clinicopathological entity in the current World Health Organization (WHO) classification and its genomic features remain sparsely characterized. We investigated a cohort of 26 cases of untreated de novo EBV-positive DLBCL of the elderly by high-resolution array-based comparative genomic profiling and fluorescence in situ hybridization (FISH). Moreover, we screened for activating mutations affecting nuclear factor (NF)-κB pathway signaling and chromatin remodeling (EZH2, CD79B, CARD11 and MYD88) due to their impact of gene expression signatures and postulated upcoming therapeutic targetability. We identified an overlap between genomic aberrations previously described to be exclusive features of plasmablastic lymphoma (PL), post-transplant lymphoproliferative disorder (PTLD) and DLBCL, respectively, indicating a close cytogenetic relationship between these entities. Few mutations affecting CD79B and CARD11 and no MYD88 mutations were detectable, hinting at EBV-mediated activation of NF-κB as an alternative to pathologically enforced B-cell receptor signaling in this rare entity.
AB - Abstract Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma (DLBCL) of the elderly constitutes a provisional clinicopathological entity in the current World Health Organization (WHO) classification and its genomic features remain sparsely characterized. We investigated a cohort of 26 cases of untreated de novo EBV-positive DLBCL of the elderly by high-resolution array-based comparative genomic profiling and fluorescence in situ hybridization (FISH). Moreover, we screened for activating mutations affecting nuclear factor (NF)-κB pathway signaling and chromatin remodeling (EZH2, CD79B, CARD11 and MYD88) due to their impact of gene expression signatures and postulated upcoming therapeutic targetability. We identified an overlap between genomic aberrations previously described to be exclusive features of plasmablastic lymphoma (PL), post-transplant lymphoproliferative disorder (PTLD) and DLBCL, respectively, indicating a close cytogenetic relationship between these entities. Few mutations affecting CD79B and CARD11 and no MYD88 mutations were detectable, hinting at EBV-mediated activation of NF-κB as an alternative to pathologically enforced B-cell receptor signaling in this rare entity.
UR - http://www.scopus.com/inward/record.url?scp=84929119156&partnerID=8YFLogxK
U2 - 10.3109/10428194.2014.944522
DO - 10.3109/10428194.2014.944522
M3 - Journal articles
C2 - 25030036
AN - SCOPUS:84929119156
SN - 1042-8194
VL - 56
SP - 1100
EP - 1106
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 4
ER -