Next-generation sequencing of immunoglobulin gene rearrangements for clonality assessment: a technical feasibility study by EuroClonality-NGS

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Authors	SCHEIJEN B. MEIJERS R.W.J. RIJNTJES J. VA NDER KLIFT M.Y. MOBS M. STEINHILBER J. REIGL Tomáš VAN DEN BRAND M. KOTROVA M. RITTER J.M. CATHERWOOD M.A. STAMATOPOULOS K. BRUGGEMANN M. DAVI F. DARZENTAS Nikos POTT C. FEND F. HUMMEL M. LANGERAK A.W. GROENEN P.J.T.A.
Year of publication	2019
Type	Article in Periodical
Magazine / Source	Leukemia
MU Faculty or unit	Central European Institute of Technology
Citation
web	https://www.nature.com/articles/s41375-019-0508-7.pdf
Doi	http://dx.doi.org/10.1038/s41375-019-0508-7
Keywords	RESIDUAL DISEASE DETECTION; B-CELL LYMPHOMA; BIOMED-2; PCR; REPERTOIRE; DIAGNOSIS; ASSAYS; DISTINGUISHES
Description	One of the hallmarks of B lymphoid malignancies is a B cell clone characterized by a unique footprint of clonal immunoglobulin (IG) gene rearrangements that serves as a diagnostic marker for clonality assessment. The EuroClonality/BIOMED-2 assay is currently the gold standard for analyzing IG heavy chain (IGH) and x light chain (IGK) gene rearrangements of suspected B cell lymphomas. Here, the EuroClonality-NGS Working Group presents a multicentre technical feasibility study of a novel approach involving next-generation sequencing (NGS) of IGH and IGK loci rearrangements that is highly suitable for detecting IG gene rearrangements in frozen and formalin-fixed paraffin-embedded tissue specimens. By employing gene-specific primers for IGH and IGK amplifying smaller amplicon sizes in combination with deep sequencing technology, this NGS -based IG clonality analysis showed robust performance, even in DNA samples of suboptimal DNA integrity, and a high clinical sensitivity for the detection of clonal rearrangements. Bioinformatics analyses of the high-throughput sequencing data with ARResT/Interrogate, a platform developed within the EuroClonality-NGS Working Group, allowed accurate identification of clonotypes in both polyclonal cell populations and monoclonal lymphoproliferative disorders. This multicentre feasibility study is an important step towards implementation of NGS -based clonality assessment in clinical practice, which will eventually improve lymphoma diagnostics.
Related projects:	CERIT Scientific Cloud Encyklopedie CLL podskupin: unikátní znalostní databáze vybavená bioinformatickými nástroji použitelná v personalizované biomedicíně a klinické praxi