ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2022
Clonality assessment and detection of clonal diversity in classic Hodgkin lymphoma by next-generation sequencing of immunoglobulin gene rearrangements.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- Longitudinal omics reveals immune repertoire remodeling in myasthenia gravis patients post-tacrolimus therapy.Genes and immunity · 2026Article
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- Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expression.Frontiers in veterinary science · 2025Article
- Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma.International journal of molecular sciences · 2024Article
- Diagnostic and prognostic molecular pathology of lymphoid malignancies.Virchows Archiv : an international journal of pathology · 2024Review
- Clonal Relationship and Mutation Analysis in Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Associated With Diffuse Large B-cell Lymphoma.HemaSphere · 2023Article
- A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma.Blood advances · 2023Article
- Editorial: The promise of immunogenetics for precision oncology.Frontiers in oncology · 2023Article
- Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside.Experimental hematology & oncology · 2022Review
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- The Need for Standardization in Next-Generation Sequencing Studies for Classic Hodgkin Lymphoma: A Systematic Review.Diagnostics (Basel, Switzerland) · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clonality 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.
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