Abstract 5097
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Funding
Association pour la Recherche contre le Cancer (ARC) Fondation pour la Recherche Médicale (FRM).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
6079 - Invasive fungal diseases in patients with Hodgkin’s lymphoma before and after allogeneic hematopoietic stem cell transplantation
Presenter: Marina Popova
Session: Poster Display session 1
Resources:
Abstract
5995 - Invasive fungal diseases caused by rare pathogens in patients after hematopoietic stem cell transplantation (HSCT) & chemotherapy
Presenter: Yuliya Rogacheva
Session: Poster Display session 1
Resources:
Abstract
2961 - Safety and pharmacokinetics of novel CXCR4 antagonist YF-H-2015005 in the mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma
Presenter: Weiping Liu
Session: Poster Display session 1
Resources:
Abstract
5771 - Chemotherapy associated Hyponatremia in Hematological Malignancies: A retrospective study of 189 patients treated in a single medical center
Presenter: Vadim Lesan
Session: Poster Display session 1
Resources:
Abstract
1165 - Risk factors for Bacteremia-Associated Mortality of Aeromona sobria in Hematologic Malignancies
Presenter: Gabriel De la Cruz-Kú
Session: Poster Display session 1
Resources:
Abstract
5287 - Use of droplet digital polymerase chain reaction for detecting minimal residual disease: a prospective, multi-institutional study
Presenter: Hyunkyung Park
Session: Poster Display session 1
Resources:
Abstract
1886 - RUBIH2 — Use of NGS in haematological malignancies: from real world data to national recommendations, an innovative program to evaluate the impact of healthcare technology on patient care
Presenter: Severine Coquerelle
Session: Poster Display session 1
Resources:
Abstract
1940 - Outcomes of chronic myeloid leukemia with T315I mutation in the absence of targeted therapy or hematopoietic stem cell transplantation
Presenter: Nageswara Palukuri
Session: Poster Display session 1
Resources:
Abstract
1946 - Is bone marrow examination indispensible in chronic myeloid Leukemia at diagnosis ?
Presenter: Nageswara Palukuri
Session: Poster Display session 1
Resources:
Abstract
1904 - Incidence of Imatinib Resistance in Chronic Myeloid Leukemia (CML) Patients: Experience from Resource Poor Centre of Eastern India
Presenter: Debmalya Bhattacharyya
Session: Poster Display session 1
Resources:
Abstract