ArticleNature genetics2021
Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 161 citations in OpenAlex.
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- The Invasive Margin of Glioblastoma as a Molecular Ecosystem: Spatial Heterogeneity, Tumor-Host Interactions, and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Therapy-Related Mutational Signatures in Subsequent Neoplasms among Survivors of Childhood Cancer.Cancer discovery · 2026Article
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- Toward a Conceptual Multiscale Framework for Predictive Radiobiology: Integrating Genomic Damage, Network Rewiring, and Tissue Microenvironment.International journal of molecular sciences · 2026Review
- CDKN2A/B status and histological grade independently predict post-recurrence survival in recurrent IDH-mutant astrocytoma.Brain tumor pathology · 2026Article
- Genomic and spatial analysis of local recurrences following risk-adapted breast radiotherapy in the IMPORT trials.Breast cancer research : BCR · 2026Article
- Therapy-associated mutagenesis at CTCF binding sites is shaped by chromatin context and DNA repair capacity.bioRxiv : the preprint server for biology · 2026Article
- TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas.Cell reports. Medicine · 2026Article
- Mutational profiles of spontaneous and radiation-related mammary carcinomas in a rat model of Brca1 haploinsufficiency.Scientific reports · 2026Article
- HAT1 as a Lactyltransferase to Promote DNA Repair Through RPA1 Lactylation in Glioblastoma.International journal of biological sciences · 2026Article
- The Evolving Role of Local Radiotherapy in the Management of Oligometastatic Non-Small Cell Lung Cancer.Cancer management and research · 2026Review
- Glioblastoma in adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.Neuro-oncology · 2025Review
- Mutagenic Impact and Evolutionary Influence of Chemoradiotherapy in Hematologic Malignancies.Blood cancer discovery · 2025Article
- Mutational Signatures in Radiation-Induced Cancer: A Review of Experimental Animal and Human Studies.Biology · 2025Review
- Distinctive molecular features of radiation-induced thyroid cancers.Science advances · 2025Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Ionizing radiation causes DNA damage and is a mainstay for cancer treatment, but understanding of its genomic impact is limited. We analyzed mutational spectra following radiotherapy in 190 paired primary and recurrent gliomas from the Glioma Longitudinal Analysis Consortium and 3,693 post-treatment metastatic tumors from the Hartwig Medical Foundation. We identified radiotherapy-associated significant increases in the burden of small deletions (5-15 bp) and large deletions (20+ bp to chromosome-arm length). Small deletions were characterized by a larger span size, lacking breakpoint microhomology and were genomically more dispersed when compared to pre-existing deletions and deletions in non-irradiated tumors. Mutational signature analysis implicated classical non-homologous end-joining-mediated DNA damage repair and APOBEC mutagenesis following radiotherapy. A high radiation-associated deletion burden was associated with worse clinical outcomes, suggesting that effective repair of radiation-induced DNA damage is detrimental to patient survival. These results may be leveraged to predict sensitivity to radiation therapy in recurrent cancer.
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