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

Frontiers in Oncology

Sylvia Ritter¹  Carola Hartel¹  Manuela Marron²  Lukas Stefan Eckhard³  Sebastian Zahnreich⁴  Danuta Galetzka⁴  Heinz Schmidberger⁴  Claudia Spix⁵  Peter Scholz-Kreisel⁶  Alicia Poplawski⁶  Thomas Hankeln⁷  Markus Löbrich⁸  Johanna Mirsch⁸ 

[1] Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany;Department of Epidemiological Methods and Etiologic Research, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany;Department of Orthopedic Surgery, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany;Department of Radiation Oncology and Radiation Therapy, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany;German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany;Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany;Institute of Organismic and Molecular Evolution, Molecular Genetics and Genome Analysis, Johannes Gutenberg University Mainz, Mainz, Germany;Radiation Biology and DNA Repair, Technical University of Darmstadt, Darmstadt, Germany;

关键词: childhood cancer;    second primary malignancies;    ionizing radiation;    chromosome aberrations;    radiation sensitivity;    spontaneous chromosomal instability;   

DOI  :  10.3389/fonc.2020.01338

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown