Molecular Classification of Endometrial Stromal Sarcomas Using RNA Sequencing Defines Nosological and Prognostic Subgroups with Different Natural History

A series of 42 patient tumors diagnosed as endometrial stromal sarcoma (ESS) based on the morphology but negative for JAZF1 and/or YWHAE rearrangement in FISH was analyzed by RNA-sequencing. A chromosomal rearrangement was identified in 31 (74%) of the cases and a missense mutation in known oncogene...

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Bibliographic Details
Published in:Cancers 2020-09, Vol.12 (9), p.2604
Main Authors: Brahmi, Mehdi, Franceschi, Tatiana, Treilleux, Isabelle, Pissaloux, Daniel, Ray-Coquard, Isabelle, Dufresne, Armelle, Vanacker, Helene, Carbonnaux, Melodie, Meeus, Pierre, Sunyach, Marie-Pierre, Bouhamama, Amine, Karanian, Marie, Meurgey, Alexandra, Blay, Jean-Yves, Tirode, Franck
Format: Article
Language:English
Subjects:
Biochemistry, Molecular Biology
Cancer
Endometrial cancer
Genetic aspects
Genomics
Life Sciences
Methods
Molecular biology
RNA sequencing
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Summary:A series of 42 patient tumors diagnosed as endometrial stromal sarcoma (ESS) based on the morphology but negative for JAZF1 and/or YWHAE rearrangement 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 a JAZF1-SUZ12 fusion, one high grade ESS harboring a BCOR-ITD, two uterine tumors resembling ovarian sex cord tumors, two samples each of uterine leiomyoma and leiomyosarcomas and a series of BCOR-rearranged family of tumor (n = 8) indicated that tumors could be gather in three distinct subgroups: one mainly composed of BCOR-rearranged samples that contained seven ESS samples, one mainly composed of JAZF1-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). While YWHAE-NUTM2 fusion genes may be present in both high and low grade ESS, the high-grade presents with additional BCOR or BCORL1 gene mutations. RNAseq brings clinically relevant molecular classification, enabling the reclassification of diseases and the guidance of therapeutic strategy.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12092604