Supplementary Table and Figure Legends from Genomic Landscape of Ewing Sarcoma Defines an Aggressive Subtype with Co-Association of STAG2 and TP53 Mutations

Tirode, Franck; Surdez, Didier; Ma, Xiaotu; Parker, Matthew; Le Deley, Marie Cécile; Bahrami, Armita; Zhang, Zhaojie; Lapouble, Eve; Grossetête-Lalami, Sandrine; Rusch, Michael; Reynaud, Stéphanie; Rio-Frio, Thomas; Hedlund, Erin; Wu, Gang; Chen, Xiang; Pierron, Gaelle; Oberlin, Odile; Zaidi, Sakina; Lemmon, Gordon; Gupta, Pankaj; Vadodaria, Bhavin; Easton, John; Gut, Marta; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Shurtleff, Sheila; Laurence, Valérie; Michon, Jean; Marec-Bérard, Perrine; Gut, Ivo; Downing, James; Dyer, Michael; Zhang, Jinghui; Delattre, Olivier

doi:10.1158/2159-8290.22530086.v1

21598290cd140622-sup-133188_1_supp_0_nbsr1p.pdf (45.15 kB)

Supplementary Table and Figure Legends from Genomic Landscape of Ewing Sarcoma Defines an Aggressive Subtype with Co-Association of STAG2 and TP53 Mutations

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posted on 2023-04-03, 20:44 authored by Franck Tirode, Didier Surdez, Xiaotu Ma, Matthew Parker, Marie Cécile Le Deley, Armita Bahrami, Zhaojie Zhang, Eve Lapouble, Sandrine Grossetête-Lalami, Michael Rusch, Stéphanie Reynaud, Thomas Rio-Frio, Erin Hedlund, Gang Wu, Xiang Chen, Gaelle Pierron, Odile Oberlin, Sakina Zaidi, Gordon Lemmon, Pankaj Gupta, Bhavin Vadodaria, John Easton, Marta Gut, Li Ding, Elaine R. Mardis, Richard K. Wilson, Sheila Shurtleff, Valérie Laurence, Jean Michon, Perrine Marec-Bérard, Ivo Gut, James Downing, Michael Dyer, Jinghui Zhang, Olivier Delattre

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ARTICLE ABSTRACT

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 STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, and ZMYM3 (2.7% each). Strikingly, STAG2 mutations and CDKN2A deletions were mutually exclusive, as confirmed in Ewing sarcoma cell lines. In an expanded cohort of 299 patients with clinical data, we discovered that STAG2 and TP53 mutations are often concurrent and are associated with poor outcome. Finally, we detected subclonal STAG2 mutations in diagnostic tumors and expansion of STAG2-immunonegative cells in relapsed tumors as compared with matched diagnostic samples.Significance: Whole-genome sequencing reveals that the somatic mutation rate in Ewing sarcoma is low. Tumors that harbor STAG2 and TP53 mutations have a particularly dismal prognosis with current treatments and require alternative therapies. Novel drugs that target epigenetic regulators may constitute viable therapeutic strategies in a subset of patients with mutations in chromatin modifiers. Cancer Discov; 4(11); 1342–53. ©2014 AACR.This article is highlighted in the In This Issue feature, p. 1243

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Dna Damage And Repair Chromosomal translocations Gene Technologies Oncogenes & Tumor Suppressors p53 Pediatric Cancers Sarcomas Soft-tissue sarcoma

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Supplementary Table and Figure Legends from Genomic Landscape of Ewing Sarcoma Defines an Aggressive Subtype with Co-Association of STAG2 and TP53 Mutations

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