Catching the driver mutations in Ewing sarcoma tumours: an in silico genomic analysis

WCRJ 2019; 6: e1321
DOI: 10.32113/wcrj_20196_1321

  Topic: Molecular oncology     Category:

Abstract

OBJECTIVE: Ewing sarcoma (EWS) is a rare neuroectodermal-related malignancy affecting bones and soft tissues. The well-known hallmark of genomic alteration in EWS is gene fusion involving the Ewing Sarcoma Breakpoint Region 1 (EWSR1) gene. However, studies have determined that this is not the sole determinant of tumour transformation and indicated the presence of other mutated genes related to signalling pathways and chromatin-modifying genes.

MATERIALS AND METHODS: This is an in silico analysis of the previously published genomic sequencing of 218 EWS patients and 11 cell lines.

RESULTS: The presence of frequent deleterious mutations in EWSR1 (17%); titin, TTN (16%); stromal antigen 2, STAG2 (14%); and tumour protein P53, TP53 (9%) was determined. An increased prevalence of the co-occurrence of a few mutated driver genes across tumour samples was significantly noted, namely, between TP53 and either EWSR1 or STAG2 and between TTN and complement C3b/C4b receptor 1 (CR1) or zinc finger homeobox 3 (ZFHX3), suggesting their joint contribution to EWS tumour development. Patients carrying the TP53 aberration alone or combined with EWSR1 or STAG2 alterations had much lower survival rates. Functional enrichment analysis highlighted transcription factors, kinases, and hub proteins that could be putative therapeutic targets for EWS in the future.

CONCLUSIONS: The current analysis provides new insights that can be used as a roadmap for future in vitro or in vivo work. A systems biology approach will be required that takes into account the genomic and epigenomic landscapes of EWS for risk stratification and future molecular targeted therapy.

To cite this article

Catching the driver mutations in Ewing sarcoma tumours: an in silico genomic analysis

WCRJ 2019; 6: e1321
DOI: 10.32113/wcrj_20196_1321

Publication History

Submission date: 08 Mar 2019

Revised on: 16 Apr 2019

Accepted on: 14 May 2019

Published online: 18 Jun 2019