Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer
Please always quote using this URN: urn:nbn:de:bvb:20-opus-141838
- Background: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. Methodology/Findings: To identify factors that may influence theBackground: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. Methodology/Findings: To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to one-cancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the two-cancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy gamma-irradiated cells of two-cancer patients. Conclusions/Significance: Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.…
Author: | Eva Weis, Holger Schoen, Anja Victor, Claudia Spix, Marco Ludwig, Brigitte Schneider-Raetzke, Nicolai Kohlschmidt, Oliver Bartsch, Aslihan Gerhold-Ay, Nils Boehm, Franz Grus, Thomas Haaf, Danuta Galetzka |
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URN: | urn:nbn:de:bvb:20-opus-141838 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Humangenetik |
Language: | English |
Parent Title (English): | PLoS ONE |
Year of Completion: | 2011 |
Volume: | 6 |
Issue: | 10 |
Pagenumber: | e25750 |
Source: | PLoS ONE 6(10): e25750. doi:10.1371/journal.pone.0025750 |
DOI: | https://doi.org/10.1371/journal.pone.0025750 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 611 Menschliche Anatomie, Zytologie, Histologie |
Tag: | Checkpoints; DNA methylation; Damage; Genes; Instability; Malignant neoplasms; Repair; Stability; Susceptibility |
Release Date: | 2019/01/21 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |