Journal
CANCERS
Volume 12, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/cancers12092604
Keywords
endometrial stromal sarcomas; RNA-sequencing; gene fusions; prognostic; uterine; sarcoma; expression profile
Categories
Funding
- NetSarc/RREPS/RESOS (INCA)
- NetSarc/RREPS/RESOS (DGOS)
- Association DAM's, Ensemble contre Le GIST [FP7-278742]
- Fondation ARC
- Infosarcome, InterSARC (INCA)
- LabEx DEvweCAN [ANR-10-LABX-0061]
- Ligue de l'Ain contre le Cancer Ligue contre le Cancer
- Institut National du Cancer [INCa-PLBIO16-208]
- LYRICAN [INCA-DGOS-INSERM 12563]
- EURACAN [EC 739521]
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Simple Summary In about half of the cases, endometrial stromal sarcomas lack the canonical oncogenic fusionsJAZF1-SUZ12orYWHAE-NUTM2, which are mutually exclusive. The aim of this study was to explore by RNA sequencing a retrospective series of uterine sarcomas diagnosed as endometrial stromal sarcomas but negative forJAZF1and/orYWHAErearrangement in FISH, in order to provide a better description of their molecular landscape, improve the classification of endometrial stromal sarcomas and provide guidance for disease management. A series of 42 patient tumors diagnosed as endometrial stromal sarcoma (ESS) based on the morphology but negative forJAZF1and/orYWHAErearrangement in FISH was analyzed by RNA-sequencing. A chromosomal rearrangement was identified in 31 (74%) of the cases and a missense mutation in known oncogenes/tumor suppressor genes in 11 (26%). Cluster analyses on the expression profiles from this series together with a control cohort composed of five samples of low grade ESS harboring aJAZF1-SUZ12fusion, one high grade ESS harboring aBCOR-ITD, two uterine tumors resembling ovarian sex cord tumors, two samples each of uterine leiomyoma and leiomyosarcomas and a series ofBCOR-rearranged family of tumor (n= 8) indicated that tumors could be gather in three distinct subgroups: one mainly composed ofBCOR-rearranged samples that contained seven ESS samples, one mainly composed ofJAZF1-fused ESS (n= 15) and the last composed of various molecular subtypes (n= 19). These three subgroups display different gene signatures, different in silico cell cycle scores and very different clinical presentations, natural history and survival (log-rank test,p= 0.004). WhileYWHAE-NUTM2fusion genes may be present in both high and low grade ESS, the high-grade presents with additionalBCORorBCORL1gene mutations. RNAseq brings clinically relevant molecular classification, enabling the reclassification of diseases and the guidance of therapeutic strategy.
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