scholarly journals Clonality assessment and detection of clonal diversity in classic Hodgkin lymphoma by next-generation sequencing of immunoglobulin gene rearrangements

2021 ◽  
Author(s):  
Diede A. G. van Bladel ◽  
Michiel van den Brand ◽  
Jos Rijntjes ◽  
Samhita Pamidimarri Naga ◽  
Demi L. C. M. Haacke ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hodgkin Lymphoma ◽  
Clonal Diversity ◽  
Gene Rearrangements ◽  
Classic Hodgkin Lymphoma ◽  
Clonality Analysis ◽  
Improved Performance ◽  
Tissue Specimens ◽  
Generation Sequencing ◽  
Clonality Assessment

AbstractClonality analysis in classic Hodgkin lymphoma (cHL) is of added value for correctly diagnosing patients with atypical presentation or histology reminiscent of T cell lymphoma, and for establishing the clonal relationship in patients with recurrent disease. However, such analysis has been hampered by the sparsity of malignant Hodgkin and Reed-Sternberg (HRS) cells in a background of reactive immune cells. Recently, the EuroClonality-NGS Working Group developed a novel next-generation sequencing (NGS)-based assay and bioinformatics platform (ARResT/Interrogate) to detect immunoglobulin (IG) gene rearrangements for clonality testing in B-cell lymphoproliferations. Here, we demonstrate the improved performance of IG-NGS compared to conventional BIOMED-2/EuroClonality analysis to detect clonal gene rearrangements in 16 well-characterized primary cHL cases within the IG heavy chain (IGH) and kappa light chain (IGK) loci. This was most obvious in formalin-fixed paraffin-embedded (FFPE) tissue specimens, where three times more clonal cases were detected with IG-NGS (9 cases) compared to BIOMED-2 (3 cases). In total, almost four times more clonal rearrangements were detected in FFPE with IG-NGS (N = 23) as compared to BIOMED-2/EuroClonality (N = 6) as judged on identical IGH and IGK targets. The same clonal rearrangements were also identified in paired fresh frozen cHL samples. To validate the neoplastic origin of the detected clonotypes, IG-NGS clonality analysis was performed on isolated HRS cells, demonstrating identical clonotypes as detected in cHL whole-tissue specimens. Interestingly, IG-NGS and HRS single-cell analysis after DEPArray™ digital sorting revealed rearrangement patterns and copy number variation profiles indicating clonal diversity and intratumoral heterogeneity in cHL. Our data demonstrate improved performance of NGS-based detection of IG gene rearrangements in cHL whole-tissue specimens, providing a sensitive molecular diagnostic assay for clonality assessment in Hodgkin lymphoma.

scholarly journals Detection of classical Hodgkin lymphoma specific sequence in peripheral blood using a next-generation sequencing approach

2015 ◽  
Vol 169 (5) ◽  
pp. 689-693 ◽  
Author(s):  
Yasuhiro Oki ◽  
Sattva S. Neelapu ◽  
Michelle Fanale ◽  
Larry W. Kwak ◽  
Luis Fayad ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
Classical Hodgkin Lymphoma ◽  
Next Generation ◽  
Specific Sequence ◽  
Generation Sequencing

Histiocytic Sarcoma Following B-Lymphoblastic Leukemia/Lymphoma

2019 ◽  
Vol 152 (4) ◽  
pp. 486-494 ◽  
Author(s):  
Julia T Geyer ◽  
Nuri Yigit ◽  
Ayako Miyaguchi ◽  
Shuhua Cheng ◽  
Joseph Casano ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Next Generation Sequencing ◽  
Lymphoblastic Leukemia ◽  
Histiocytic Sarcoma ◽  
Divergent Evolution ◽  
Gene Rearrangements ◽  
Intensive Chemotherapy ◽  
Whole Exome ◽  
Common Precursor ◽  
Generation Sequencing

AbstractObjectivesRare cases of clonally related histiocytic sarcoma (HS) following B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) have been reported to date.MethodsWe present a patient with HS, which appeared as a breast mass 12 months after the initial diagnosis of B-ALL.ResultsBoth HS and the B-ALL shared IGH-MYC and IGK gene rearrangements. Next-generation sequencing and whole-exome sequencing (WES) studies detected 35 common mutations, as well as mutations unique to B-ALL (16) and HS (15), including BRAF D594G. The patient achieved complete remission of B-ALL, but HS failed to respond to many cycles of intensive chemotherapy regimens. A partial response was achieved with sorafenib, a BRAF-targeted therapy.ConclusionsTo our knowledge, this is the first study to demonstrate by WES that clonally related B-ALL and HS arise through divergent evolution from a common precursor. We present our findings together with a discussion of the previously reported cases of HS in patients with B-ALL.

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