Transcriptome characterization of radiation-induced sarcomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE102055 | GEO | 2019/06/28
REPOSITORIES: GEO
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Project description:Post-radiation sarcomas are rare secondary cancers arising from radiation therapies. To date, few genetic specificities have been described for such malignancies and the oncogenesis of sarcomas with complex genetics (both sporadic and post-radiation) remains largely misunderstood. We performed genomic analyses on both sporadic and post-radiation sarcomas to study their copy-number alterations. This analysis is described in Lesluyes et al. 2019 (PMID: 31243333).
2020-07-17 | GSE154591 | GEO
Project description:Genomic comparison of post-radiation versus sporadic sarcomas
| PRJNA646742 | ENA
Project description:Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume. These mice were then monitored for the remainder of their lifespan and a large number of T cell lymphomas were analysed, alongside those arising in mice exposed to equivalent doses of standard Cs137 gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikaros, Pten, Trp53 and Bcl11b genes we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. 32 unique tumours (12 gamma ray-induced, 20 carbon ion-induced) each with sex-matched reference DNA
2015-03-03 | E-GEOD-61315 | biostudies-arrayexpress
Project description:Soft-tissue tumours are derived from mesenchymal cells such as fibroblasts, muscle cells, or adipocytes, but for many such tumours the histogenesis is controversial. We aimed to start molecular characterisation of these rare neoplasms and to do a genome-wide search for new diagnostic markers. We analysed gene-expression patterns of 41 soft-tissue tumours with spotted cDNA microarrays. After removal of errors introduced by use of different microarray batches, the expression patterns of 5520 genes that were well defined were used to separate tumours into discrete groups by hierarchical clustering and singular value decomposition. Synovial sarcomas, gastrointestinal stromal tumours, neural tumours, and a subset of the leiomyosarcomas, showed strikingly distinct gene-expression patterns. Other tumour categories--malignant fibrous histiocytoma, liposarcoma, and the remaining leiomyosarcomas--shared molecular profiles that were not predicted by histological features or immunohistochemistry. Strong expression of known genes, such as KIT in gastrointestinal stromal tumours, was noted within gene sets that distinguished the different sarcomas. However, many uncharacterised genes also contributed to the distinction between tumour types. These results suggest a new method for classification of soft-tissue tumours, which could improve on the method based on histological findings. Large numbers of uncharacterised genes contributed to distinctions between the tumours, and some of these could be useful markers for diagnosis, have prognostic significance, or prove possible targets for treatment.
2005-09-26 | E-SMDB-1380 | biostudies-arrayexpress
Project description:Purpose: Patients with advanced soft-tissue sarcomas (STSs) exhibit a poor prognosis and have few therapeutic options. DNA-dependent protein kinase catalytic subunit (DNA-PK) is a multifunctional serine—threonine protein kinase that plays a crucial role in DNA double-strand damage repair via nonhomologous end joining (NHEJ). Experimental design: To investigate the therapeutic potential of DNA-PK targeting in STS, we first evaluated the prognostic value of DNA-PK expression in two large cohorts of patients with STS. We then used the potent and selective DNA-PK inhibitor AZD7648 compound to investigate the antitumor effect of the pharmacological inhibition of DNA-PK in vitro via MTT, apoptosis, cell cycle, and proliferation assays. In vivo studies were performed with patient-derived xenograft models to evaluate the effects of AZD7648 in combination with chemotherapy or ionizing radiation on tumor growth. The mechanisms of sensitivity and resistance to DNA-PK inhibition were investigated by using a genome-wide CRISPR-Cas9 positive screen. Results: DNA-PK overexpression is significantly associated with poor prognosis in patients with sarcomas. Selective pharmacological inhibition of DNA-PK strongly synergizes with radiation- and doxorubicin-based regimen in sarcoma models. By using a genome-wide CRISPR-Cas9 positive screen, we identified genes involved in sensitivity to DNA-PK inhibition. Conclusion: DNA-PK inhibition deserves clinical investigation to improve response to current therapies in patients with sarcoma
2023-09-25 | GSE243758 | GEO
Project description:Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume. These mice were then monitored for the remainder of their lifespan and a large number of T cell lymphomas were analysed, alongside those arising in mice exposed to equivalent doses of standard Cs137 gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikaros, Pten, Trp53 and Bcl11b genes we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed.
2015-03-03 | GSE61315 | GEO
Project description:Genomic signature of the ionizing radiation effect in sarcomas developed in the field of irradiation after radiotherapy
2012-06-08 | E-MEXP-3248 | biostudies-arrayexpress
Project description:Transcriptome signature of the ionizing radiation effect in sarcomas developed in the field of irradiation after radiotherapy
2011-03-31 | E-MEXP-2687 | biostudies-arrayexpress
Project description:transcriptome comparison of radiation-induced papillary thyroid carcinomas with sporadic papillary thyroid carcinomas
2005-10-27 | E-MEXP-485 | biostudies-arrayexpress
Project description:Abstract: Despite impressive responses in some patients, immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Nearly all preclinical immunotherapy studies utilize transplant tumor models, but cure rates of transplant tumors treated with immunotherapy overestimate patient responses. Here, we show that transplant sarcomas are cured by PD-1 blockade and radiotherapy, but identical treatment fails in autochthonous sarcomas, which demonstrate tumor-specific immune tolerance. We characterize tumor-infiltrating immune cells from transplant and primary tumors and reveal striking differences in their immune landscapes. Although radiotherapy remodels myeloid cells in primary and transplant sarcomas, only transplant tumors are enriched for activated CD8+ T cells associated with tumor clearance. By CIBERSORTx, the immune microenvironment of primary sarcomas in mice transcriptionally resembles most human sarcomas, while transplant sarcomas model the most inflamed sarcomas in patients. These results identify distinct microenvironments in murine sarcomas that coevolve with the immune system and suggest that patients whose sarcomas have an immune phenotype similar to transplant tumors may benefit most from PD-1 blockade and radiotherapy.
2020-10-21 | GSE148856 | GEO