Aggressive genomic features in clinically indolent primary HHV8-negative effusion-based lymphoma

Mendeville, Matías; Roemer, Margaretha G.M.; Hout, Mari F.C.M. van den; Vries, G Tjitske Los-de; Bladergroen, Reno S.; Stathi, Phylicia; Hijmering, Nathalie J.; Rosenwald, Andreas; Ylstra, Bauke; Jong, Daphne de

doi:10.1182/blood-2017-12-822171

Cited by 25 publications

(22 citation statements)

References 24 publications

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“…Cytogenetically, trisomy 8 has been reported in certain cases of PEBL. 12 , 16 , 17 , 23 , 28 , 29 Our patient likely possesses trisomy 8 as FISH testing revealed three copies of MYC with negative staining for MYC on immunostaining.…”

Section: Discussionmentioning

confidence: 82%

Primary HHV-8 (-) Effusion-Based Non-Germinal Center B Cell Diffuse Large B Cell Lymphoma Successfully Treated with Standard Anthracycline-Based Chemoimmunotherapy

Kuhlman

Moustafa

Jiang

et al. 2021

JBM

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Effusion-based lymphomas (EBL) are usually high-grade B cell non-Hodgkin’s lymphomas which involve effusion fluid in a body cavity, typically presenting as a pleural effusion, without evidence of disease elsewhere. They are most frequently seen in HIV-infected individuals and are biologically driven by human herpesvirus-8 virus (HHV-8). HHV-8 (+) EBL is recognized as primary effusion lymphoma (PEL) under the World Health Organization classification. HHV-8 (-) EBL has been reported in association with Hepatitis C virus (HCV) infection, Epstein-Barr virus (EBV) infection, fluid overload, liver cirrhosis, renal dysfunction, cardiac arrhythmias, myocardial infarction, and heart failure. These cases can be labeled as primary EBL (PEBL). We describe a non-germinal center B cell diffuse large B cell lymphoma (NGCB-DLBCL) presenting as PEBL in an immunocompetent 81-year-old male who had an extensive cardiac history and tested negative for HIV, HHV-8, and EBV. He was treated with thoracentesis and standard anthracycline-based chemoimmunotherapy and has remained in complete remission for over 5 ½ years since his original diagnosis. Our case indicates that NGCB-DLBCL can present as PEBL and is potentially curable with the standard chemoimmunotherapeutic approach.

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Section: Discussionmentioning

confidence: 82%

Primary HHV-8 (-) Effusion-Based Non-Germinal Center B Cell Diffuse Large B Cell Lymphoma Successfully Treated with Standard Anthracycline-Based Chemoimmunotherapy

Kuhlman

Moustafa

Jiang

et al. 2021

JBM

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“…We also wished to compare FFPE-TLC to the targeted DNA capture-based sequencing methods (Capture-NGS) for the detection and analysis of structural variants in FFPE specimens 8 – 10 . For this, we compared Capture-NGS and FFPE-TLC performance on 19 FFPE samples that were part of a larger cohort of >200 FFPE samples previously analyzed by Capture-NGS.…”

Section: Resultsmentioning

confidence: 99%

“…More recently, next-generation sequencing (NGS) DNA capture methods have been introduced for rearrangement detection in selected gene panels in FFPE samples, which makes it possible to detect breakpoints at base-pair resolution and identify translocation partner genes 7 – 10 . However, such methods rely on capturing unambiguous fusion-reads, which can be challenging when non-unique sequences flank the breakpoint 11 .…”

Section: Introductionmentioning

confidence: 99%

Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing

et al. 2021

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In routine diagnostic pathology, cancer biopsies are preserved by formalin-fixed, paraffin-embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis, and treatment. Here, we present FFPE-targeted locus capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and previously uncharacterized rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens.

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“…2 Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. 3 Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. 4 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…The outcomes of DLBCL patients are variable and therefore stratification into low-risk and high-risk groups is helpful for planning therapy. The development of body cavity effusions in DLBCL is often an indication of a significant pathologic process [ 2 ], and previous studies have shown the adverse impact of malignant lymphoma-associated effusions (direct infiltration or distant metastasis) on survival in DLBCL patients [ 3 , 4 ]. Others have reported that DLBCL patients with tumorous effusions bear an even worse prognosis than patients with stage IV disease without effusions [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Aggressive genomic features in clinically indolent primary HHV8-negative effusion-based lymphoma

Cited by 25 publications

References 24 publications

Primary HHV-8 (-) Effusion-Based Non-Germinal Center B Cell Diffuse Large B Cell Lymphoma Successfully Treated with Standard Anthracycline-Based Chemoimmunotherapy

Primary HHV-8 (-) Effusion-Based Non-Germinal Center B Cell Diffuse Large B Cell Lymphoma Successfully Treated with Standard Anthracycline-Based Chemoimmunotherapy

Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing

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

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