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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Krumbholz M, Woessmann W, Zierk J, Seniuk D, Ceppi P, Zimmermann M, Singh VK, Metzler M, Damm-Welk C
Zeitschrift: Oncotarget
Jahr der Veröffentlichung: 2018
Band: 9
Heftnummer: 41
Seitenbereich: 26543-26555
ISSN: 1949-2553


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.


FAU-Autoren / FAU-Herausgeber

Ceppi, Paolo Dr.
Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe I Dr.Körner
Krumbholz, Manuela Dr. rer. nat.
Kinder- und Jugendklinik
Metzler, Markus PD Dr.
Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie
Zierk, Jakob Dr. med.
Kinder- und Jugendklinik


Autor(en) der externen Einrichtung(en)
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
Kerckhoff-Klinik


Zitierweisen

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://dx.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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Zuletzt aktualisiert 2019-25-04 um 14:57