Characterization and diagnostic application of genomic NPM-ALK fusion sequences in anaplastic large-cell lymphoma

Krumbholz M, Woessmann W, Zierk J, Seniuk D, Ceppi P, Zimmermann M, Singh VK, Metzler M, Damm-Welk C (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Oncotarget Impact Journals

Book Volume: 9

Pages Range: 26543-26555

Journal Issue: 41

DOI: 10.18632/oncotarget.25489

Abstract

Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) fusion genes resulting from the translocation t(2;5)(p23;q35) are present in almost 90% of childhood ALK-positive anaplastic large-cell lymphomas (ALCL). Detection and quantification of minimal disseminated disease (MDD) by measuring NPM-ALK fusion transcript levels in the blood provide independent prognostic parameters. Characterization of the genomic breakpoints provides insights into the pathogenesis of the translocation and allows for DNA-based minimal disease monitoring. We designed a nested multiplex PCR assay for identification and characterization of genomic NPM-ALK fusion sequences in 45 pediatric ALCL-patients, and used the sequences for quantitative MDD monitoring. Breakpoint analysis indicates the involvement of inaccurate non-homologous end joining repair mechanisms in the formation of NPM-ALK fusions. Parallel quantification of RNA and DNA levels in the cellular fraction of 45 blood samples from eight patients with NPM-ALK-positive ALCL correlated, as did cell-free circulating NPM-ALK DNA copies in the plasma fraction of 37 blood samples. With genomic NPM-ALK fusion sequence quantification, plasma samples of ALCL patients become an additional source for MRD-assessment. Parallel quantification of NPM-ALK transcripts and fusion genes in ALCL cell lines treated with the ALK kinase inhibitor crizotinib illustrates the potential value of supplementary DNA-based quantification in particular clinical settings.

Authors with CRIS profile

Manuela Krumbholz Department of Paediatrics and Adolescent Medicine Jakob Zierk Department of Paediatrics and Adolescent Medicine Paolo Ceppi Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 1 Prof. Dr. Ceppi Markus Metzler Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Kerckhoff-Klinik DE Germany (DE)

How to cite

APA:

Krumbholz, M., Woessmann, W., Zierk, J., Seniuk, D., Ceppi, P., Zimmermann, M.,... Damm-Welk, C. (2018). Characterization and diagnostic application of genomic NPM-ALK fusion sequences in anaplastic large-cell lymphoma. Oncotarget, 9(41), 26543-26555. https://doi.org/10.18632/oncotarget.25489

MLA:

Krumbholz, Manuela, et al. "Characterization and diagnostic application of genomic NPM-ALK fusion sequences in anaplastic large-cell lymphoma." Oncotarget 9.41 (2018): 26543-26555.

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