Molecular classification of endometrial stromal sarcomas using RNA sequencing defines nosological and prognostic subgroups with different natural history

Autor: Marie Karanian, Alexandra Meurgey, Franck Tirode, Pierre Meeus, Isabelle Ray-Coquard, Tatiana Franceschi, Amine Bouhamama, Mehdi Brahmi, Isabelle Treilleux, Armelle Dufresne, Mélodie Carbonnaux, Daniel Pissaloux, Jean-Yves Blay, Hélène Vanacker, Marie-Pierre Sunyach
Přispěvatelé: Département d'Oncologie Médicale [Lyon] ( Centre Léon Bérard), Centre Léon Bérard [Lyon], Service de Pathologie [Centre Leon Berard], Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'anatomopathologie, biopathologie, Département de Radio-Oncologie [CLB, Lyon] (Centre Léon Bérard), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), TIRODE, Franck
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
Stromal cell
sarcoma
RNA-sequencing
[SDV.CAN]Life Sciences [q-bio]/Cancer
Chromosomal rearrangement
Biology
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Prognostic
lcsh:RC254-282
Article
Fusion gene
03 medical and health sciences
0302 clinical medicine
[SDV.CAN] Life Sciences [q-bio]/Cancer
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
medicine
Missense mutation
YWHAE
Gene
Endometrial stromal sarcoma
Gene fusions
uterine
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
expression profile
030104 developmental biology
Oncology
Endometrial stromal sarcomas
030220 oncology & carcinogenesis
Cancer research
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Sarcoma
Zdroj: Cancers
Cancers, MDPI, In press, 12 (9), pp.2604. ⟨10.3390/cancers12092604⟩
Volume 12
Issue 9
Cancers, MDPI, In press
Cancers, Vol 12, Iss 2604, p 2604 (2020)
Cancers, In press, 12 (9), pp.2604. ⟨10.3390/cancers12092604⟩
ISSN: 2072-6694
DOI: 10.3390/cancers12092604⟩
Popis: 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. Abstract 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.
Databáze: OpenAIRE
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