The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 2 of 37
Back to Result List

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.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
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
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):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung