دورية أكاديمية
Gene expression variability in long-term survivors of childhood cancer and cancer-free controls in response to ionizing irradiation
| العنوان: | Gene expression variability in long-term survivors of childhood cancer and cancer-free controls in response to ionizing irradiation |
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| المؤلفون: | Grandt, Caine Lucas, Brackmann, Lara Kim, Foraita, Ronja, Schwarz, Heike, Hummel-Bartenschlager, Willempje, Hankeln, Thomas, Kraemer, Christiane, Zahnreich, Sebastian, Drees, Philipp, Mirsch, Johanna, Spix, Claudia, Blettner, Maria, Schmidberger, Heinz, Binder, Harald, Hess, Moritz, Galetzka, Danuta, Marini, Federico, Poplawski, Alicia, Marron, Manuela |
| المصدر: | http://lobid.org/resources/991000067219706485Test#!, 29(1):41. |
| سنة النشر: | 2023 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | Kikme study, Pan-cancer, NGS, RNA-Seq, Radiation response, Childhood cancer, High dose, Low dose |
| الوصف: | BACKGROUND: Differential expression analysis is usually adjusted for variation. However, most studies that examined the expression variability (EV) have used computations affected by low expression levels and did not examine healthy tissue. This study aims to calculate and characterize an unbiased EV in primary fibroblasts of childhood cancer survivors and cancer-free controls (N0) in response to ionizing radiation. METHODS: Human skin fibroblasts of 52 donors with a first primary neoplasm in childhood (N1), 52 donors with at least one second primary neoplasm (N2 +), as well as 52 N0 were obtained from the KiKme case–control study and exposed to a high (2 Gray) and a low dose (0.05 Gray) of X-rays and sham- irradiation (0 Gray). Genes were then classified as hypo-, non-, or hyper-variable per donor group and radiation treatment, and then examined for over-represented functional signatures. RESULTS: We found 22 genes with considerable EV differences between donor groups, of which 11 genes were associated with response to ionizing radiation, stress, and DNA repair. The largest number of genes exclusive to one donor group and variability classification combination were all detected in N0: hypo-variable genes after 0 Gray (n = 49), 0.05 Gray (n = 41), and 2 Gray (n = 38), as well as hyper-variable genes after any dose (n = 43). While after 2 Gray positive regulation of cell cycle was hypo-variable in N0, (regulation of) fibroblast proliferation was over-represented in hyper-variable genes of N1 and N2+. In N2+, 30 genes were uniquely classified as hyper-variable after the low dose and were associated with the ERK1/ERK2 cascade. For N1, no exclusive gene sets with functions related to the radiation response were detected in our data. CONCLUSION: N2+ showed high degrees of variability in pathways for the cell fate decision after genotoxic insults that may lead to the transfer and multiplication of DNA-damage via proliferation, where apoptosis and removal of the damaged genome would have been appropriate. Such a ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://repository.publisso.de/resource/frl:6452805Test; https://doi.org/10.1186/s10020-023-00629-2Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061869Test/; https://molmed.biomedcentral.com/articles/10.1186/s10020-023-00629-2#Sec27Test |
| DOI: | 10.1186/s10020-023-00629-2 |
| DOI: | 10.1186/s10020-023-00629-2#Sec27 |
| الإتاحة: | https://doi.org/10.1186/s10020-023-00629-2Test https://repository.publisso.de/resource/frl:6452805Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061869Test/ |
| حقوق: | CC BY 4.0 |
| رقم الانضمام: | edsbas.A751072D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s10020-023-00629-2 |
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