Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines
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 wi...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55340-5 |
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| author | Merve Kasan Florian H. Geyer Jana Siebenlist Martin Sill Rupert Öllinger Tobias Faehling Enrique de Álava Didier Surdez Uta Dirksen Ina Oehme Katia Scotlandi Olivier Delattre Martina Müller-Nurasyid Roland Rad Konstantin Strauch Thomas G. P. Grünewald Florencia Cidre-Aranaz |
| author_facet | Merve Kasan Florian H. Geyer Jana Siebenlist Martin Sill Rupert Öllinger Tobias Faehling Enrique de Álava Didier Surdez Uta Dirksen Ina Oehme Katia Scotlandi Olivier Delattre Martina Müller-Nurasyid Roland Rad Konstantin Strauch Thomas G. P. Grünewald Florencia Cidre-Aranaz |
| author_sort | Merve Kasan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-497e714d13fb4bfd8bdef6c539a4e9a1 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-497e714d13fb4bfd8bdef6c539a4e9a12025-01-05T12:37:02ZengNature PortfolioNature Communications2041-17232025-01-011611910.1038/s41467-024-55340-5Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell linesMerve Kasan0Florian H. Geyer1Jana Siebenlist2Martin Sill3Rupert Öllinger4Tobias Faehling5Enrique de Álava6Didier Surdez7Uta Dirksen8Ina Oehme9Katia Scotlandi10Olivier Delattre11Martina Müller-Nurasyid12Roland Rad13Konstantin Strauch14Thomas G. P. Grünewald15Florencia Cidre-Aranaz16Hopp Children’s Cancer Center (KiTZ)Hopp Children’s Cancer Center (KiTZ)Hopp Children’s Cancer Center (KiTZ)Hopp Children’s Cancer Center (KiTZ)TranslaTUM, Center for Translational Cancer Research, Technical University of MunichHopp Children’s Cancer Center (KiTZ)Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONCINSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research CenterDepartment of Pediatrics, University Hospital EssenHopp Children’s Cancer Center (KiTZ)Experimental Oncology Laboratory, IRCCS Istituto Ortopedico RizzoliINSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research CenterInstitute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg UniversityTranslaTUM, Center for Translational Cancer Research, Technical University of MunichInstitute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg UniversityHopp Children’s Cancer Center (KiTZ)Hopp Children’s Cancer Center (KiTZ)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.https://doi.org/10.1038/s41467-024-55340-5 |
| spellingShingle | Merve Kasan Florian H. Geyer Jana Siebenlist Martin Sill Rupert Öllinger Tobias Faehling Enrique de Álava Didier Surdez Uta Dirksen Ina Oehme Katia Scotlandi Olivier Delattre Martina Müller-Nurasyid Roland Rad Konstantin Strauch Thomas G. P. Grünewald Florencia Cidre-Aranaz Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines Nature Communications |
| title | Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines |
| title_full | Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines |
| title_fullStr | Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines |
| title_full_unstemmed | Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines |
| title_short | Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines |
| title_sort | genomic and phenotypic stability of fusion driven pediatric sarcoma cell lines |
| url | https://doi.org/10.1038/s41467-024-55340-5 |
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