Next-generation antigen receptor sequencing of paired diagnosis and relapse samples of B-cell acute lymphoblastic leukemia: Clonal evolution and implications for minimal residual disease target selection
| Autor: | Prisca M J Theunissen, Valerie de Haas, Vincent H.J. van der Velden, Andrew P. Stubbs, David van Zessen, Maaike de Bie |
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| Přispěvatelé: | Immunology, Pathology |
| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
Neoplasm Residual Receptors Antigen B-Cell Biology Polymerase Chain Reaction Somatic evolution in cancer DNA sequencing Clonal Evolution 03 medical and health sciences 0302 clinical medicine Recurrence Precursor B-Cell Lymphoblastic Leukemia-Lymphoma hemic and lymphatic diseases Antigen receptor Humans Gene Rearrangement B-Lymphocyte Gene Selection (genetic algorithm) High-Throughput Nucleotide Sequencing Hematology B-cell acute lymphoblastic leukemia Minimal residual disease Oncology 030220 oncology & carcinogenesis Cancer research Clone (B-cell biology) 030215 immunology |
| Zdroj: | Leukemia Research, 76, 98-104. Elsevier Ltd. |
| ISSN: | 0145-2126 |
| Popis: | Antigen receptor gene rearrangements are frequently applied as molecular targets for detection of minimal residual disease (MRD) in B-cell precursor acute lymphoblastic leukemia patients. Since such targets may be lost at relapse, appropriate selection of antigen receptor genes as MRD-PCR target is critical. Recently, next-generation sequencing (NGS) - much more sensitive and quantitative than classical PCR-heteroduplex approaches - has been introduced for identification of MRD-PCR targets. We evaluated 42 paired diagnosis-relapse samples by NGS (IGH, IGK, TRG, TRD, and TRB) to evaluate clonal evolution patterns and to design an algorithm for selection of antigen receptor gene rearrangements most likely to remain stable at relapse. Overall, only 393 out of 1446 (27%) clonal rearrangements were stable between diagnosis and relapse. If only index clones with a frequency >5% at diagnosis were taken into account, this number increased to 65%; including only index clones with an absolute read count >10,000, indicating truly major clones, further increased the stability to 84%. Over 90% of index clones at relapse were also present as index clone at diagnosis. Our data provide detailed information about the stability of antigen receptor gene rearrangements, based on which we propose an algorithm for selecting stable MRD-PCR targets, successful in >97% of patients. |
| Databáze: | OpenAIRE |
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