Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines

Merve Kasan, Florian H. Geyer, Jana Siebenlist, Martin Sill, Rupert Öllinger, Tobias Faehling, Enrique Álava, Didier Surdez, Uta Dirksen, Ina Oehme, Katia Scotlandi, Olivier Delattre, Martina Müller-Nurasyid, Roland Rad, Konstantin Strauch, Thomas G. P. Grünewald and Florencia Cidre-Aranaz ()
Additional contact information
Merve Kasan: Hopp Children’s Cancer Center (KiTZ)
Florian H. Geyer: Hopp Children’s Cancer Center (KiTZ)
Jana Siebenlist: Hopp Children’s Cancer Center (KiTZ)
Martin Sill: Hopp Children’s Cancer Center (KiTZ)
Rupert Öllinger: Technical University of Munich
Tobias Faehling: Hopp Children’s Cancer Center (KiTZ)
Enrique Álava: Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC
Didier Surdez: Institut Curie Research Center
Uta Dirksen: University Hospital Essen
Ina Oehme: Hopp Children’s Cancer Center (KiTZ)
Katia Scotlandi: IRCCS Istituto Ortopedico Rizzoli
Olivier Delattre: Institut Curie Research Center
Martina Müller-Nurasyid: Johannes Gutenberg University
Roland Rad: Technical University of Munich
Konstantin Strauch: Johannes Gutenberg University
Thomas G. P. Grünewald: Hopp Children’s Cancer Center (KiTZ)
Florencia Cidre-Aranaz: Hopp Children’s Cancer Center (KiTZ)

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: Abstract Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. Here, we hypothesize that oligomutated pediatric sarcoma cell lines mainly driven by a fusion transcription factor, such as Ewing sarcoma (EwS), are genetically and phenotypically more stable than the previously investigated adult carcinoma cell lines. A comprehensive molecular and phenotypic characterization of multiple EwS cell line strains, together with a simultaneous analysis during 12 months of continuous cell culture show that fusion-driven pediatric sarcoma cell line strains are genomically more stable than adult carcinoma strains, display remarkably stable and homogenous transcriptomes, and exhibit uniform and stable drug response. Additionally, the analysis of multiple EwS cell lines subjected to long-term continuous culture reveals that variable degrees of genomic/transcriptomic/phenotypic changes among fusion-driven cell lines, further exemplifying that the potential for reproducibility of in vitro scientific results may be rather understood as a spectrum, even within the same tumor entity.

Date: 2025
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DOI: 10.1038/s41467-024-55340-5

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