Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 1

5097 - Fusion of immortalized myoblasts induces genomic instability that drives tumor development and progression.


28 Sep 2019


Poster Display session 1


Tumour Site

Soft Tissue Sarcomas


Candice Merle


Annals of Oncology (2019) 30 (suppl_5): v683-v709. 10.1093/annonc/mdz283


C. Merle1, J. Baud2, N. Thebaud1, T. Lesluyes1, G. Pérot1, L. Delespaul1, L. Lartigue2, F. Chibon1

Author affiliations

  • 1 Inserm U1037, Cancer Research Center in Toulouse (CRCT), 31037 - Toulouse/FR
  • 2 Inserm U1218, Bergonie Institute, 33076 - Bordeaux/FR


Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 5097


Sarcoma are a heterogeneous group of tumor which can be split into two subgroups with distinct genetics. Half of sarcoma presents an important genomic reorganization correlated to tumor aggressiveness. At this stage, the origin of this instability is still unknown. Cell fusion is a physiological mechanism involved in several processes including myoblast differentiation and already described to be involved in aneuploidy generation and genomic instability. We thus hypothesized that cell fusion could participate to sarcoma oncogenesis by generating genomic instability.


We established cell line of hybrids from spontaneous fusion of immortalized myoblasts. Tumor and metastasis development were evaluated upon grafting and whole genome and transcriptome sequencing with in-vitro mechanistic studies were performed to decipher phenotypes acquired by hybrids upon fusion.


In vitro hybrid cell lines show a more aggressive phenotype than parental cell lines by increasing proliferation and clonogenic capacities. Only hybrids form tumors upon grafting and may develop also metastasis. Aneuploidy triggered by cell fusion induces genome reorganization and in vivo tumor genome show alterations corresponding to those observed in human rhabdomyosarcoma. Indeed, 85% of hybrid tumors harbor DMD deletions as observed in sarcoma with myogenic origin. The study of this protein reveals that tumors lose the expression of Dp427 isoform which is the one reported as a tumor suppressor. This malignant transformation of hybrids is associated to transcriptomic remodeling toward a decrease of the expression of genes involved in muscle differentiation.


To our knowledge, this is the first model able to reproduce the complex genomic of sarcoma. The detection of those hybrid cells in sarcoma tumor allowed us to push forward they are involved in sarcoma development and progression and their quantification in tumors or in circulating cells could thus establish an early prognostic marker. Finally, specific therapeutic targeting of this hybrids could represent new approach.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Frederic Chibon.


Association pour la Recherche contre le Cancer (ARC) Fondation pour la Recherche Médicale (FRM).


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.