The clinical heterogeneity of round cell sarcomas with EWSR1/FUS gene fusions: Impact of gene fusion type on clinical features and outcome.
Adolescent
Adult
Aged
Biomarkers, Tumor
/ genetics
Bone Neoplasms
/ genetics
Cells, Cultured
Child
Child, Preschool
Female
Humans
Infant
Male
Middle Aged
Oncogene Fusion
Oncogene Proteins, Fusion
/ genetics
RNA-Binding Protein EWS
/ genetics
RNA-Binding Protein FUS
/ genetics
Sarcoma, Ewing
/ genetics
Survival Analysis
EWSR1
FUS
Ewing sarcoma
Ewing-like sarcoma
gene fusions
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
25
03
2020
revised:
16
04
2020
accepted:
20
04
2020
pubmed:
4
5
2020
medline:
7
7
2021
entrez:
4
5
2020
Statut:
ppublish
Résumé
The genetic hallmark of classic Ewing sarcoma is a recurrent fusion between EWSR1 and FUS gene with a member of the ETS transcription factor family. In contrast, tumors with non-ETS gene partners have been designated until recently "Ewing-like sarcoma," as a provisional molecular entity, as their clinical and pathologic features were still evolving. However, this group was reclassified as "round cell sarcoma with EWSR1-non-ETS fusions" in the latest 2020 WHO classification. Moreover, round cell sarcomas with either CIC or BCOR gene abnormalities, initially classified under Ewing family of tumors, are now regarded as stand-alone pathologic entities based on their distinct features. In this study we investigated the clinical characteristics of 226 confirmed Ewing sarcoma patients (EWSR1-FLI1 [n = 176], EWSR1/FUS-ERG [n = 35], EWSR1/FUS-FEV [n = 12], and EWSR1-ETV1/4 [n = 3]) and 14 round cell sarcoma patients with EWSR1-non-ETS fusion (EWSR1/FUS-NFATC2 [n = 10], EWSR1-PATZ1 [n = 3], and EWSR1-VEZF1 [n = 1]). The impact on overall survival (OS) was assessed in 90 patients with available follow-up, treated between 2011 and 2018. Patients with fusions involving FEV and NFATC2 genes showed an older median age at diagnosis, compared to those with EWSR1-FLI1 (P = .005), while extraskeletal location was more common in tumors with noncanonical EWSR1-FLI1 fusions (P = .001). Axial and pelvic primary sites were more common in patients with EWSR1-FLI1 (72%), while tumors with NFATC2 fusions were more frequent in the limb (78%, P = .006). The 3-year OS in patients with EWSR1-FLI1 was 91%, compared to only 60% in patients with alternative fusions (P = .037); the latter group showing a higher rate of metastases at presentation. However, this OS difference was not significant in patients with localized tumor (P = .585). Our study demonstrates significant correlations between fusion subtype and age at presentation, primary tumor sites, and OS, in both conventional Ewing sarcoma and round cell sarcoma with EWSR1-non ETS fusions patients. Larger studies are needed to determine survival differences in localized tumors.
Identifiants
pubmed: 32362012
doi: 10.1002/gcc.22857
pmc: PMC7372700
mid: NIHMS1601067
doi:
Substances chimiques
Biomarkers, Tumor
0
EWSR1 protein, human
0
FUS protein, human
0
Oncogene Proteins, Fusion
0
RNA-Binding Protein EWS
0
RNA-Binding Protein FUS
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
525-534Subventions
Organisme : NCI NIH HHS
ID : P50 CA217694
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA140146
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals, Inc.
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