Dataset Information

Genomic landscape of Ewing sarcoma (ICGC project)

ABSTRACT: The Ewing sarcoma project aims to sequence 100 complete genomes of cells of patients suffering from this disease. It is an initiative of great projection, since this is the second most common bone tumor in children and teenagers. The goal of the project is to establish the catalogue of somatic mutations that may cooperate with EWS-ETS fusion in the development of the tumor. The Ewing sarcoma project aims to perform 100 whole genome sequencing of germline and tumor DNA as well as at least 50 RNA-seq from tumors. Correlations between molecular profiles and clinical features will be established. The mutated genes will be further validated in a series of 500 Ewing sarcoma cases from our Tumor Bank.

PROVIDER: EGAS00001000855 | EGA |

REPOSITORIES: EGA

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Publications

Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations.

Tirode Franck F Surdez Didier D Ma Xiaotu X Parker Matthew M Le Deley Marie Cécile MC Bahrami Armita A Zhang Zhaojie Z Lapouble Eve E Grossetête-Lalami Sandrine S Rusch Michael M Reynaud Stéphanie S Rio-Frio Thomas T Hedlund Erin E Wu Gang G Chen Xiang X Pierron Gaelle G Oberlin Odile O Zaidi Sakina S Lemmon Gordon G Gupta Pankaj P Vadodaria Bhavin B Easton John J Gut Marta M Ding Li L Mardis Elaine R ER Wilson Richard K RK Shurtleff Sheila S Laurence Valérie V Michon Jean J Marec-Bérard Perrine P Gut Ivo I Downing James J Dyer Michael M Zhang Jinghui J Delattre Olivier O

Cancer discovery 20140915 11

<h4>Unlabelled</h4>Ewing sarcoma is a primary bone tumor initiated by EWSR1-ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants, and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in ...[more]

PMID: 25223734

Publication: 1/3

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Project description:Tumor: tumor microenvironment (TME) interactions are critical for tumor progression and the composition and structure of the local extracellular matrix (ECM) are key determinants of tumor metastasis. We recently reported that activation of Wnt/beta- catenin signaling in Ewing sarcoma cells induces widespread transcriptional changes that are associated with acquisition of a metastatic tumor phenotype. Significantly, ECM protein-encoding genes were found to be enriched among Wnt/beta-catenin induced transcripts, leading us to hypothesize that activation of canonical Wnt signaling might induce changes in the Ewing sarcoma secretome. To address this hypothesis, conditioned media from Ewing sarcoma cell lines cultured in the presence or absence of Wnt3a was collected for proteomic analysis. Label-free mass spectrometry was used to identify and quantify differentially secreted proteins. We then used in silico databases to identify only proteins annotated as secreted. Comparison of the secretomes of two Ewing sarcoma cell lines revealed numerous shared proteins, as well as a degree of heterogeneity, in both basal and Wnt-stimulated conditions. Gene set enrichment analysis of secreted proteins revealed that Wnt stimulation reproducibly resulted in increased secretion of proteins involved in ECM organization, ECM receptor interactions, and collagen formation. In particular, Wnt-stimulated Ewing sarcoma cells upregulated secretion of structural collagens, as well as matricellular proteins, such as the metastasis-associated protein, tenascin C (TNC). Interrogation of published databases confirmed reproducible correlations between Wnt/beta-catenin activation and TNC and COL1A1 expression in patient tumors. In summary, this first study of the Ewing sarcoma secretome reveals that Wnt/beta-catenin activated tumor cells upregulate secretion of ECM proteins. Such Wnt/beta-catenin mediated changes are likely to impact on tumor: TME interactions that contribute to metastatic progression.

Dataset Information

Genomic landscape of Ewing sarcoma (ICGC project)

Publications

Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations.

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