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New Cell lines Expanding the Diversity of Ewing Sarcoma Models - methylation

ABSTRACT: Ewings sarcoma (EwS) is a highly aggressive, malignant, solid tumor of childhood and adolescence. Most EwS develop in bone, while it originates from connective, adipose or muscle tissue less frequently. We report the establishment of new human EwS cell lines, all of which carry a t(11;22) (q24;q12) translocation generating the oncogenic transcription factor EWSR1::FLI1. Sequencing of the chimeric mRNAs indicated genomic DNA breakpoints localized in intron 8 of the EWSR1 gene and 3 different introns of translocation partner gene FLI1. While three EwS cell lines carry the EWSR1::FLI1 fusions of ex7/ex6 (type I) or ex7/ex5 (type II), the EWSR1::FLI1 fusion variant ex7/ex7 (type IV) is described for the first time in a continuous EwS model. The cell lines presented genomic, epigenomic and transcriptomic stability over a period of six months, though some variations in the chromosomal aberrations were observed in one cell line. Transcriptome and epigenome were stable over time and there was only little variation between the novel EwS cell lines. The TP53 mutational status seemed to have the biggest impact on drug sensitivity profiles. The new EwS models presented here may help to identify small molecule inhibitors that act directly on EWSR1::FLI1 fusion proteins or uncover other genetic vulnerabilities of the altered epigenome and transcriptome in EwS, which would contribute to a better understanding of Ewing sarcoma tumorigenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE289061 | GEO | 2025/08/22

REPOSITORIES: GEO

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New Cell lines Expanding the Diversity of Ewing Sarcoma Models – Affymetrix Data

Project description:Ewings sarcoma (EwS) is a highly aggressive, malignant, solid tumor of childhood and adolescence. Most EwS develop in bone, while it originates from connective, adipose or muscle tissue less frequently. We report the establishment of new human EwS cell lines, all of which carry a t(11;22) (q24;q12) translocation generating the oncogenic transcription factor EWSR1::FLI1. Sequencing of the chimeric mRNAs indicated genomic DNA breakpoints localized in intron 8 of the EWSR1 gene and 3 different introns of translocation partner gene FLI1. While three EwS cell lines carry the EWSR1::FLI1 fusions of ex7/ex6 (type I) or ex7/ex5 (type II), the EWSR1::FLI1 fusion variant ex7/ex7 (type IV) is described for the first time in a continuous EwS model. The cell lines presented genomic, epigenomic and transcriptomic stability over a period of six months, though some variations in the chromosomal aberrations were observed in one cell line. Transcriptome and epigenome were stable over time and there was only little variation between the novel EwS cell lines. The TP53 mutational status seemed to have the biggest impact on drug sensitivity profiles. The new EwS models presented here may help to identify small molecule inhibitors that act directly on EWSR1::FLI1 fusion proteins or uncover other genetic vulnerabilities of the altered epigenome and transcriptome in EwS, which would contribute to a better understanding of Ewing sarcoma tumorigenesis.

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