Abstract 3029
Background
About half of ESS do not harbor a JAZF1 or YWHAE fusion and other rearrangements have already been reported. With the aim to provide a comprehensive description of the molecular landscape of endometrial stromal sarcomas (ESS), we investigated by RNA-sequencing a series of tumors diagnosed as ESS based on the morphology but negative for JAZF1 and/or YWHAE in FISH experiments.
Methods
This study was performed between September 2017 and December 2018 as a Centre Léon Bérard monocentric retrospective translational research program on tumor samples from an investigational cohort of 43 ESS patients. For clustering analyses, we used a control cohort composed of 19 patient samples of BCOR-rearranged sarcomas (n = 8), low-grade ESS with JAZF1-SUZ12 fusion (n = 5), high-grade ESS carrying a BCOR internal tandem duplication (n = 1), uterine leiomyoma (n = 2) and uterine leiomyosarcomas (n = 3). RNA sequencing was performed from FFPE material in all cases using TruSeq RNA Access Library Prep Kit (Illumina®).
Results
A chromosomal rearrangement was identified in 74% of the cases (n = 32). We identified biologically homogeneous groups of tumors such as the JAZF1-fused (to PHF1 and SYNGAP1) and the BCOR-rearranged (BCOR-ITD, ZC3H7B-BCOR, CREBBP-BCOR). Using a clustering approach on transcriptomic data, tumors were divided in 3 subgroups: one mainly composed of BCOR-rearranged ESS (n = 7), one mainly composed of JAZF1-fused ESS (n = 14) and one composed of various molecular subtypes (n = 22). This 3 subgroups display significantly different survivals (Log-rank test, p = 0.004). Five cases which harbored a YWAHE-NUTM2B fusions clustered separately: 3 cases in the group of indolent tumors (JAZF1-fused ESS) and 2 cases in the group of aggressive tumors (BCOR-rearranged sarcomas). Of note, those 2 cases harbored also a single nucleotide variant, one on BCOR and one on BCORL1. Results of RNA-seq and clustering analysis have allowed a better classification in 6 cases.
Conclusions
This is the largest series of RNAseq performed in a very rare subtype of tumors: ESS. We report new and recurrent molecular variants of ESS including previously unreported fusions. RNA-sequencing may support the diagnosis of ESS and help a better classification.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
InterSARC grants.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3181 - Effects of Three Products in the Prevention and Treatment of Chemotherapy and Radiation Therapy-Induced Oral Mucositis
Presenter: Francesca Zannier
Session: Poster Display session 1
Resources:
Abstract
2433 - Boiling Histotripsy-induced Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers
Presenter: Cheol-Hee Shin
Session: Poster Display session 1
Resources:
Abstract
2663 - The bacterial receptor NOD2 mediates LGR5+ intestinal stem cells protection against irradiation via mitophagy activation
Presenter: Antonin Levy
Session: Poster Display session 1
Resources:
Abstract
3213 - Pulse mode irradiation regimen of PDT results in high progression free and overall survival in mice with model tumor
Presenter: Alexey Bogdanov
Session: Poster Display session 1
Resources:
Abstract
3722 - Proton-sensitizing effect of small molecule inhibitor of P300 histone acetyltransferase C646 in human pancreatic cancer cells.
Presenter: Sungwon Shin
Session: Poster Display session 1
Resources:
Abstract
5805 - Red-Blood-Cell-Membrane-Enveloped Magnetic Nanoclusters as a Biomimetic Theranostic Nanoplatform for Bimodal Imaging Guided Cancer Photothermal Therapy
Presenter: sheng wang
Session: Poster Display session 1
Resources:
Abstract
5251 - Urine cell-free and extracellular vesicle cargo miRNAs as biomarkers for prostate cancer diagnosis
Presenter: Ivan Zaporozhchenko
Session: Poster Display session 1
Resources:
Abstract
3657 - Parkin, APEX1 and BCL2L1 Tissue Expression in Southern Brazilian Patients with Different Breast Cancer Molecular Subtypes
Presenter: Bianca Cabral
Session: Poster Display session 1
Resources:
Abstract
2839 - Obesity and prognosis in breast cancer
Presenter: Noha Ibrahim
Session: Poster Display session 1
Resources:
Abstract
5132 - SIPA1 is a modulator of HGF induced tumor metastasis via the regulation of tight junctions in lung adenocarcinoma cells
Presenter: Chang Liu
Session: Poster Display session 1
Resources:
Abstract