The epigenomics of sarcoma

Nacev, Benjamin A.; Jones, Kevin B.; Intlekofer, Andrew M.; Yu, Jamie S.E.; Allis, C. David; Tap, William D.; Ladanyi, Marc; Nielsen, Torsten O.

doi:10.1038/s41568-020-0288-4

Cited by 162 publications

(133 citation statements)

References 212 publications

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“…We have critically evaluated the PAX3-FOXO1 fusion oncogene with respect to categorical properties intrinsic to the pioneer class of transcription factors. Advances in recent years have encouraged integrations across fields including pediatric oncology, genomics, and the biophysics of pioneer transcription factors ( 2, 6, 12 ). Our studies have revealed that for two pioneer factors fused as a chimera in a rare childhood tumor, chromatin recognition is consistent with PF function across the genome.…”

Section: Resultsmentioning

confidence: 99%

Pioneer activity of an oncogenic fusion transcription factor at inaccessible chromatin

Sunkel

Wang

LaHaye

et al. 2020

Preprint

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Recent advances in the characterization of pioneer factors have led to new questions about domain structures and chromatin recognition. Seemingly separate fields have integrated common scientific problems with the identification of fusion pioneer factor (PF) pairs in childhood cancers. Excitingly, this represents a convergence of fields within science, of pediatric oncology, genomics, epigenetics, and biophysics. With PF-pairs emerging as driver oncogenes in childhood rhabdomyosarcoma (RMS), our studies investigate these fusion genes as a gestalt phenomenon, where the whole might equal more than the sum of the parts. We developed a new method for ChIP-seq with per-cell normalization (pc-ChIP-seq) to simultaneously define genome size and PAX3-FOXO1 localization in RMS. We report novel pioneer function for the major driver oncogene in RMS, with nucleosome-motif targeting and kinetic displacement of nucleosomes in human cells.

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Section: Resultsmentioning

confidence: 99%

Pioneer activity of an oncogenic fusion transcription factor at inaccessible chromatin

Sunkel

Wang

LaHaye

et al. 2020

Preprint

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“…The genetics of ES is relatively simple and are driven by chromosomal translocations leading to fusion oncogenes [27]. The oncogene EWS-FLI1 plays as an aberrant transcription factor which is enhanced by its interaction with several molecular partners.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Key Genes and Regulatory Elements in Ewing Sarcoma With Prognostic Values

Li¹,

Li²,

Zong³

et al. 2021

Preprint

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Background: Ewing sarcoma (ES) is one of the most common types of round cell mesenchymal neoplasms related to children and young adults. It is characterized by chromosomal translocations. However, that does not completely explain the ES proliferation and development. Methods: Several public data series (GSE45544, GSE68591, and GSE68776) were used to identify differentially expressed genes (DEGs) between ES and normal tissue. Furthermore, functional enrichment analysis and protein-protein interaction network of DEGs were performed. The regulatory network of DEGs and hub genes, survival analysis of hub genes was visualized. In addition, functional predictions of the candidate gene were analyzed. Results: A total of 142 DEGs 10 hub genes were identified. While out of them, only one candidate gene FGF7 was found to be suitable as a candidate gene. Conclusions: In conclusion, the DEGs, hub genes, and their regulatory molecules screened out in this research could contribute to comprehend the mechanisms in ES and provide potential research molecular for further study.

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“…Combining existing sarcoma nomograms with transcriptomic signatures may further improve accuracy of risk assessment 79 . Additionally, integration of gene expression analysis with other Omic profiling methodologies, such as proteomics and DNA methylation analysis, is also likely to improve prognostication with new biomarker-directed treatment opportunities [80][81][82][83] .…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Predictive and prognostic transcriptomic biomarkers in soft tissue sarcomas

et al. 2021

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Soft tissue sarcomas (STS) are rare and heterogeneous tumours comprising over 80 different histological subtypes. Treatment options remain limited in advanced STS with high rates of recurrence following resection of localised disease. Prognostication in clinical practice relies predominantly on histological grading systems as well as sarcoma nomograms. Rapid developments in gene expression profiling technologies presented opportunities for applications in sarcoma. Molecular profiling of sarcomas has improved our understanding of the cancer biology of these rare cancers and identified potential novel therapeutic targets. In particular, transcriptomic signatures could play a role in risk classification in sarcoma to aid prognostication. Unlike other solid and haematological malignancies, transcriptomic signatures have not yet reached routine clinical use in sarcomas. Herein, we evaluate early developments in gene expression profiling in sarcomas that laid the foundations for transcriptomic signature development. We discuss the development and clinical evaluation of key transcriptomic biomarker signatures in sarcomas, including Complexity INdex in SARComas (CINSARC), Genomic Grade Index, and hypoxia-associated signatures. Prospective validation of these transcriptomic signatures is required, and prospective trials are in progress to evaluate reliability for clinical application. We anticipate that integration of these gene expression signatures alongside existing prognosticators and other Omics methodologies, including proteomics and DNA methylation analysis, could improve the identification of ‘high-risk’ patients who would benefit from more aggressive or selective treatment strategies. Moving forward, the incorporation of these transcriptomic prognostication signatures in clinical practice will undoubtedly advance precision medicine in the routine clinical management of sarcoma patients.

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The epigenomics of sarcoma

Cited by 162 publications

References 212 publications

Pioneer activity of an oncogenic fusion transcription factor at inaccessible chromatin

Pioneer activity of an oncogenic fusion transcription factor at inaccessible chromatin

Comprehensive Analysis of Key Genes and Regulatory Elements in Ewing Sarcoma With Prognostic Values

Predictive and prognostic transcriptomic biomarkers in soft tissue sarcomas

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