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Genomic comparison of post-radiation versus sporadic sarcomas

ABSTRACT: Genomic comparison of post-radiation versus sporadic sarcomas

PROVIDER: PRJNA646742 | ENA |

REPOSITORIES: ENA

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Genomic comparison of post-radiation versus sporadic sarcomas

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

Transcriptome characterization of radiation-induced sarcomas

Project description:We performed RNA sequencing on secondary sarcomas, arising from previous radiation therapies. We investigated whether such radiation-induced tumours harbour specific genomic and/or transcriptomic alterations compared to sporadic (primary) sarcomas.

2019-06-28 | GSE102055 | GEO

Proteomics analysis of primary mouse sarcomas post radiation therapy

Project description:- We revealed that inhibition of glutamine metabolism via genetic deletion or pharmacological inhibition of glutaminase (Gls1) radiosensitizes primary sarcomas in vivo. To delineate the potential mechanism(s) of radiosensitization post radiation therapy (RT), we performed proteomic analysis of Gls1+/+ and Gls1fl/flsarcomas 48 hours post 10 Gy RT. We found that 490 and 217 proteins were differentially expressed in Gls1fl/flsarcomas post 0 Gy and 10 Gy compared to Gls1+/+ sarcomas, respectively. Hallmark pathway analysis revealed that Gls1 deletion with or without RT decreased the expression of protein related to proliferation and translation (E2F targets and G2M checkpoint). Interestingly, Gls1 deletion post-RT increased innate immune response marked by elevated interferon-alpha, interferon-gamma, and natural killer (NK) cell responses. Flow cytometry analysis further validated these findings and showed significantly elevated NK cells, but not dendritic and myeloid cells in primary Gls1-deficient sarcomas compared to Gls1-proficient sarcomas post-RT. Collectively, proteomic and flow cytometry datasets suggested that innate immune response is partly accountable for radiosensitizing Gls1-deficient sarcomas.

2024-06-03 | PXD050936 | Pride

Transcription profiling of sporadic and radiation-induced papillary carcinomas

Project description:transcriptome comparison of radiation-induced papillary thyroid carcinomas with sporadic papillary thyroid carcinomas

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Selective DNA-PK inhibition enhances chemotherapy and ionizing radiation activity in soft-tissue sarcomas

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

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Transcription profiling by array of human sarcomas developed in the field of irradiation after radiotherapy.

Project description:Transcriptome signature of the ionizing radiation effect in sarcomas developed in the field of irradiation after radiotherapy

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Genomic profiling by SNParray of human sarcomas developed in the field of irradiation after radiotherapy

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

A transcriptome signature distinguished sporadic from postradiotherapy radiation-induced sarcomas.

Project description:Exposure to ionizing radiation is a known risk factor for cancer. However, up to now, rigorously defined scientific criteria that could establish case-by-case the radiation-induced (RI) origin of a tumour have been lacking. To identify genes that could constitute a RI signature, we compared the transcriptome of 12 sarcomas arising in the irradiation field of a primary tumour following radiotherapy with the transcriptome of 12 sporadic sarcomas. This learning/training set contained four leiomyosarcomas, four osteosarcomas and four angiosarcomas in each subgroup. We identified a signature of 135 genes discriminating RI from sporadic sarcomas. The robustness of this signature was tested by the blind case-by-case classification of an independent set of 36 sarcomas of various histologies. Thirty-one sarcomas were classified as RI or sporadic; it was not possible to propose an aetiology for the five others. After the code break, it was found that one sporadic sarcoma was misclassified as RI. Thus, the signature is robust with a sensitivity of 96%, a positive and a negative predictive value of 96 and 100%, respectively and a specificity of 62%. The functions of the genes of the signature suggest that RI sarcomas were subject to chronic oxidative stress probably due to mitochondrial dysfunction.

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Selective DNA-PK inhibition enhances chemotherapy and ionizing radiation activity in soft-tissue sarcomas

Project description:Selective DNA-PK inhibition enhances chemotherapy and ionizing radiation activity in soft-tissue sarcomas

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