Previous studies have shown that lymphomatous effusions in patients with diffuse large B-cell lymphoma (DLBCL) are linked with a considerably poor prognosis, even worse than for non-effusion-associated patients with stage IV disease. Researchers of a study published in Biomarker Research postulated that certain genetic abnormalities are correlated with lymphomatous effusions. Confirming such would help to identify related pathways, oncogenic mechanisms, and therapeutic targets.
In this study, researchers compared whole-exome sequencing on DLBCL solid organs samples (n = 22) involving nine effusions. They then developed a mutational accumulation-based approach which they utilized to score each gene. They employed mutation interpreters to discern candidate pathogenic genes associated with lymphomatous effusions. Furthermore, they performed gene-set enrichment analysis to extract the related pathways.
According to the results, the genes involved in identified pathways with high accumulation scores in the effusion based DLBCL cases were associated with migration/invasion. The researchers noted that they successfully validated expression of eight selected genes in DLBCL cell lines and clinical samples (MUC4, SLC35G6, TP53BP2, ARAP3, IL13RA1, PDIA4, HDAC1, and MDM2) and validated expression of three proteins (MUC4, HDAC1 and MDM2) in an independent cohort of DLBCL cases with (n = 31) and without (n = 20) lymphomatous effusions.
“We found that overexpression of HDAC1 and MDM2 correlated with the presence of lymphomatous effusions, and HDAC1 overexpression was associated with the poorest prognosis,” the researchers wrote of the results.
The researchers concluded that these findings “suggest that DLBCL associated with lymphomatous effusions may be associated mechanistically with TP53-MDM2 pathway and HDAC-related chromatin remodeling mechanisms.”