ArticleNature communications2019
Cooperation of cancer drivers with regulatory germline variants shapes clinical outcomes.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 69 citations in OpenAlex.
- A Practical Compass to Biological Digital Resources and Omics Integration in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Analysis of Colony Formation Capacity in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Genetic and Epigenetic Manipulation Using CRISPR Techniques in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Application of Resazurin and ATP Detection Cell Viability Assays for Drug Sensitivity Screening in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Proliferation Assessment by Trypan Blue Exclusion in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Germline Variation and Somatic Alterations in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Epigenetic modulation of prostate cancer disparities in men with African ancestry.Nature reviews. Urology · 2026Review
- Zinc-dependent Zip7-MAZ-MYBL2 axis promotes prostate cancer metastasis.Communications biology · 2026Article
- The hegemonic EWSR1::ETS oncoprotein overrules core regulatory circuitry principles in Ewing sarcoma.NPJ precision oncology · 2025Article
- Regulation ofBiology · 2025Article
- Cell cycle regulator MYBL2 is a distinct vulnerability in acute myeloid leukemia.Cell death discovery · 2025Article
- EWS::FLI1-DHX9 interaction promotes Ewing sarcoma sensitivity to DNA topoisomerase 1 poisons by altering R-loop metabolism.Oncogene · 2025Article
- Targeting metastasis in paediatric bone sarcomas.Molecular cancer · 2025Review
- Article
- Revisiting CDKN2A dysregulation in Ewing sarcoma.Molecular oncology · 2025Article
- Somatic mutation phasing and haplotype extension using linked-reads in multiple myeloma.bioRxiv : the preprint server for biology · 2024Article
- Germline determinants of aberrant signaling pathways in cancer.NPJ precision oncology · 2024Article
- Genome-wide binding analysis unveils critical implication of B-Myb-mediated transactivation in cancers.International journal of biological sciences · 2024Article
- The MYBL2-CCL2 axis promotes tumor progression and resistance to anti-PD-1 therapy in ovarian cancer by inducing immunosuppressive macrophages.Cancer cell international · 2023Article
- Molecular and biologic biomarkers of Ewing sarcoma: A systematic review.Journal of bone oncology · 2023Review
Corrections and comments
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Authors and funding
31 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pediatric malignancies including Ewing sarcoma (EwS) feature a paucity of somatic alterations except for pathognomonic driver-mutations that cannot explain overt variations in clinical outcome. Here, we demonstrate in EwS how cooperation of dominant oncogenes and regulatory germline variants determine tumor growth, patient survival and drug response. Binding of the oncogenic EWSR1-FLI1 fusion transcription factor to a polymorphic enhancer-like DNA element controls expression of the transcription factor MYBL2 mediating these phenotypes. Whole-genome and RNA sequencing reveals that variability at this locus is inherited via the germline and is associated with variable inter-tumoral MYBL2 expression. High MYBL2 levels sensitize EwS cells for inhibition of its upstream activating kinase CDK2 in vitro and in vivo, suggesting MYBL2 as a putative biomarker for anti-CDK2-therapy. Collectively, we establish cooperation of somatic mutations and regulatory germline variants as a major determinant of tumor progression and highlight the importance of integrating the regulatory genome in precision medicine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.