دورية أكاديمية
Radiation-response in primary fibroblasts of long-term survivors of childhood cancer with and without second primary neoplasms: The KiKme study
| العنوان: | Radiation-response in primary fibroblasts of long-term survivors of childhood cancer with and without second primary neoplasms: The KiKme study |
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| المؤلفون: | Grandt, Caine Lucas, Brackmann, Lara Kim, Poplawski, Alicia, Schwarz, Heike, Hummel-Bartenschlager, Willempje, Hankeln, Thomas, Kraemer, Christane, Marini, Federico, Zahnreich, Sebastian, Schmitt, Iris, Drees, Philipp, Mirsch, Johanna, Grabow, Desiree, Schmidberger, Heinz, Binder, Harald, Hess, Moritz, Galetzka, Danuta, Marron, Manuela |
| المصدر: | Molecular medicine, 28(1):105 |
| سنة النشر: | 2022 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | Radiation experiment, NGS, RNA-Seq, Radiation response, Diferential gene expression, High dose, Low dose, Pathway analysis |
| الوصف: | BACKGROUND: The etiology and most risk factors for a sporadic first primary neoplasm in childhood or subsequent second primary neoplasms are still unknown. One established causal factor for therapy-associated second primary neoplasms is the exposure to ionizing radiation during radiation therapy as a mainstay of cancer treatment. Second primary neoplasms occur in 8% of all cancer survivors within 30 years after the first diagnosis in Germany, but the underlying factors for intrinsic susceptibilities have not yet been clarified. Thus, the purpose of this nested case–control study was the investigation and comparison of gene expression and affected pathways in primary fibroblasts of childhood cancer survivors with a first primary neoplasm only or with at least one subsequent second primary neoplasm, and controls without neoplasms after exposure to a low and a high dose of ionizing radiation. METHODS: Primary fibroblasts were obtained from skin biopsies from 52 adult donors with a first primary neoplasm in childhood (N1), 52 with at least one additional primary neoplasm (N2+), as well as 52 without cancer (N0) from the KiKme study. Cultured fibroblasts were exposed to a high [2 Gray (Gy)] and a low dose (0.05 Gy) of X-rays. Messenger ribonucleic acid was extracted 4 h after exposure and Illumina-sequenced. Differentially expressed genes (DEGs) were computed using limma for R, selected at a false discovery rate level of 0.05, and further analyzed for pathway enrichment (right-tailed Fisher’s Exact Test) and (in-) activation (z ≥|2|) using Ingenuity Pathway Analysis. RESULTS: After 0.05 Gy, least DEGs were found in N0 (n = 236), compared to N1 (n = 653) and N2+ (n = 694). The top DEGs with regard to the adjusted p-value were upregulated in fibroblasts across all donor groups (SESN1, MDM2, CDKN1A, TIGAR, BTG2, BLOC1S2, PPM1D, PHLDB3, FBXO22, AEN, TRIAP1, and POLH). Here, we observed activation of p53 Signaling in N0 and to a lesser extent in N1, but not in N2+. Only in N0, DNA (excision-) repair (involved genes: ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://repository.publisso.de/resource/frl:6438343Test; https://doi.org/10.1186/s10020-022-00520-6Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450413Test/; https://molmed.biomedcentral.com/articles/10.1186/s10020-022-00520-6#Sec22Test |
| DOI: | 10.1186/s10020-022-00520-6 |
| DOI: | 10.1186/s10020-022-00520-6#Sec22 |
| الإتاحة: | https://doi.org/10.1186/s10020-022-00520-6Test https://repository.publisso.de/resource/frl:6438343Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450413Test/ |
| حقوق: | CC BY 4.0 |
| رقم الانضمام: | edsbas.C6F69D39 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s10020-022-00520-6 |
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