Universität zu Köln

Rieh, Lara, Mulaw, Medhanie, Kneer, Katharina, Beer, Meinhard, Beer, Ambros, Bart, Thomas F., Benes, Vladimir, Schulte, Johannes, Fischer, Matthias, Debatin, Klaus-Michael ORCID: 0000-0002-8397-1886 and Beltinger, Christian (2023). Targeted parallel DNA sequencing detects circulating tumor-associated variants of the mitochondrial and nuclear genomes in patients with neuroblastoma. Cancer Rep.-US, 6 (1). HOBOKEN: WILEY. ISSN 2573-8348

Full text not available from this repository.

Abstract

Background The utility for liquid biopsy of tumor-associated circulating single-nucleotide variants, as opposed to mutations, of the mitochondrial (mt) and nuclear genomes in neuroblastoma (NB) is unknown. Procedure Variants of the mt and nuclear genomes from tumor, blood cells, and consecutive plasma samples of five patients with metastatic NB that relapsed or progressed were analyzed. Targeted parallel sequencing results of the mt genome, and of the coding region of 139 nuclear genes and 22 miRNAs implicated in NB, were correlated with clinical imaging and laboratory data. Results All tumors harbored multiple somatic mt and nuclear single nucleotide variants with low allelic frequency, most of them not detected in the circulation. In one patient a tumor-associated mt somatic variant was detected in the plasma before and during progressive disease. In a second patient a circulating nuclear tumor-associated DNA variant heralded clinical relapse. In all patients somatic mt and nuclear variants not evident in the tumor biopsy at time of diagnosis were found circulating at varying timepoints. This suggests either tumor heterogeneity, evolution of tumor variants or a confounding contribution of normal tissues to somatic variants in patient plasma. The number and allelic frequency of the circulating variants did not reflect the clinical course of the tumors. Mutational signatures of mt and nuclear somatic variants differed. They varied between patients and were detected in the circulation without mirroring the patients' course. Conclusions In this limited cohort of NB patients clinically informative tumor-associated mt and nuclear circulating variants were detected by targeted parallel sequencing in a minority of patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rieh, Lara UNSPECIFIED UNSPECIFIED UNSPECIFIED Mulaw, Medhanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kneer, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Beer, Meinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Beer, Ambros UNSPECIFIED UNSPECIFIED UNSPECIFIED Bart, Thomas F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benes, Vladimir UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulte, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Debatin, Klaus-Michael UNSPECIFIED orcid.org/0000-0002-8397-1886 UNSPECIFIED Beltinger, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-687985
DOI:	10.1002/cnr2.1687
Journal or Publication Title:	Cancer Rep.-US
Volume:	6
Number:	1
Date:	2023
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2573-8348
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACTIVATING MUTATIONS; MYCN-AMPLIFICATION; GENETIC LANDSCAPE; ALK KINASE; PREDISPOSITION; REARRANGEMENTS; PREDICTION; SIGNATURES; FREQUENT; VOLUME Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68798