TY - JOUR
T1 - Next-generation sequencing of immunoglobulin gene rearrangements for clonality assessment
T2 - a technical feasibility study by EuroClonality-NGS
AU - Scheijen, Blanca
AU - Meijers, Ruud W J
AU - Rijntjes, Jos
AU - van der Klift, Michèle Y
AU - Möbs, Markus
AU - Steinhilber, Julia
AU - Reigl, Tomas
AU - van den Brand, Michiel
AU - Kotrová, Michaela
AU - Ritter, Julia-Marie
AU - Catherwood, Mark A
AU - Stamatopoulos, Kostas
AU - Brüggemann, Monika
AU - Davi, Frédéric
AU - Darzentas, Nikos
AU - Pott, Christiane
AU - Fend, Falko
AU - Hummel, Michael
AU - Langerak, Anton W
AU - Groenen, Patricia J T A
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/9
Y1 - 2019/9
N2 - 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 κ 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.
AB - 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 κ 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.
KW - Feasibility Studies
KW - Gene Rearrangement/genetics
KW - Genes, Immunoglobulin/genetics
KW - High-Throughput Nucleotide Sequencing/methods
KW - Humans
KW - Immunoglobulin Heavy Chains/genetics
KW - Immunoglobulin kappa-Chains/genetics
KW - Lymphoma, B-Cell/genetics
KW - Lymphoproliferative Disorders/genetics
UR - http://www.scopus.com/inward/record.url?scp=85067857244&partnerID=8YFLogxK
U2 - 10.1038/s41375-019-0508-7
DO - 10.1038/s41375-019-0508-7
M3 - Article
C2 - 31197258
SN - 0887-6924
VL - 33
SP - 2227
EP - 2240
JO - Leukemia
JF - Leukemia
IS - 9
ER -