Deciphering genes associated with diffuse large B-cell lymphoma with lymphomatous effusions: A mutational accumulation scoring approach

Sina Abdollahi, Seyedeh Zahra Dehghanian, Liang Yi Hung, Shiang Jie Yang, Dao Peng Chen, L. Jeffrey Medeiros, Jung Hsien Chiang, Kung Chao Chang

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)

摘要

Introduction: Earlier studies have shown that lymphomatous effusions in patients with diffuse large B-cell lymphoma (DLBCL) are associated with a very poor prognosis, even worse than for non-effusion-associated patients with stage IV disease. We hypothesized that certain genetic abnormalities were associated with lymphomatous effusions, which would help to identify related pathways, oncogenic mechanisms, and therapeutic targets. Methods: We compared whole-exome sequencing on DLBCL samples involving solid organs (n = 22) and involving effusions (n = 9). We designed a mutational accumulation-based approach to score each gene and used mutation interpreters to identify candidate pathogenic genes associated with lymphomatous effusions. Moreover, we performed gene-set enrichment analysis from a microarray comparison of effusion-associated versus non-effusion-associated DLBCL cases to extract the related pathways. Results: We found that genes involved in identified pathways or with high accumulation scores in the effusion-based DLBCL cases were associated with migration/invasion. We validated expression of 8 selected genes in DLBCL cell lines and clinical samples: MUC4, SLC35G6, TP53BP2, ARAP3, IL13RA1, PDIA4, HDAC1 and MDM2, and validated expression of 3 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. Conclusion: Our findings suggest that DLBCL associated with lymphomatous effusions may be associated mechanistically with TP53-MDM2 pathway and HDAC-related chromatin remodeling mechanisms.

原文English
文章編號74
期刊Biomarker Research
9
發行號1
DOIs
出版狀態Published - 2021 12月

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 臨床生物化學
  • 生物化學(醫學)

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