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Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms

Zahnreich, Sebastian ; Poplawski, Alicia ; Hartel, Carola ; Eckhard, Lukas Stefan ; Galetzka, Danuta ; Hankeln, Thomas ; Löbrich, Markus ; Marron, Manuela ; Mirsch, Johanna ; Ritter, Sylvia ; Scholz-Kreisel, Peter ; Spix, Claudia ; Schmidberger, Heinz (2021):
Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms. (Publisher's Version)
In: Frontiers in Oncology, 10, Frontiers, e-ISSN 2234-943X,
DOI: 10.26083/tuprints-00018936,
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Item Type: Article
Origin: Secondary publication service
Status: Publisher's Version
Title: Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms
Language: English
Abstract:

The purpose of the present study was to investigate whether former childhood cancer patients who developed a subsequent secondary primary neoplasm (SPN) are characterized by elevated spontaneous chromosomal instability or cellular and chromosomal radiation sensitivity as surrogate markers of compromised DNA repair compared to childhood cancer patients with a first primary neoplasm (FPN) only or tumor-free controls. Primary skin fibroblasts were obtained in a nested case-control study including 23 patients with a pediatric FPN, 22 matched patients with a pediatric FPN and an SPN, and 22 matched tumor-free donors. Clonogenic cell survival and cytogenetic aberrations in Giemsa-stained first metaphases were assessed after X-irradiation in G1 or on prematurely condensed chromosomes of cells irradiated and analyzed in G2. Fluorescence in situ hybridization was applied to investigate spontaneous transmissible aberrations in selected donors. No significant difference in clonogenic survival or the average yield of spontaneous or radiation-induced aberrations was found between the study populations. However, two donors with an SPN showed striking spontaneous chromosomal instability occurring as high rates of numerical and structural aberrations or non-clonal and clonal translocations. No correlation was found between radiation sensitivity and a susceptibility to a pediatric FPN or a treatment-associated SPN. Together, the results of this unique case-control study show genomic stability and normal radiation sensitivity in normal somatic cells of donors with an early and high intrinsic or therapy-associated tumor risk. These findings provide valuable information for future studies on the etiology of sporadic childhood cancer and therapy-related SPN as well as for the establishment of predictive biomarkers based on altered DNA repair processes.

Journal or Publication Title: Frontiers in Oncology
Journal volume: 10
Publisher: Frontiers
Collation: 16 Seiten
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 16 Aug 2021 12:15
Last Modified: 16 Aug 2021 12:16
DOI: 10.26083/tuprints-00018936
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-189369
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/18936
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