Back to Search Start Over

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

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
Source :
Cancers; Sep2020, Vol. 12 Issue 9, p2604, 1p
Publication Year :
2020

Abstract

Simple Summary: In about half of the cases, endometrial stromal sarcomas lack the canonical oncogenic fusions JAZF1-SUZ12 or YWHAE-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 for JAZF1 and/or YWHAE rearrangement 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 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20726694
Volume :
12
Issue :
9
Database :
Complementary Index
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
146538704
Full Text :
https://doi.org/10.3390/cancers12092604