Kasan Merve, Geyer Florian H, Siebenlist Jana, Sill Martin, Öllinger Rupert, Faehling Tobias, de Álava Enrique, Surdez Didier, Dirksen Uta, Oehme Ina, Scotlandi Katia, Delattre Olivier, Müller-Nurasyid Martina, Rad Roland, Strauch Konstantin, Grünewald Thomas G P, Cidre-Aranaz Florencia
Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Division of Translational Pediatric Sarcoma Research (B410), German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
Nat Commun. 2025 Jan 3;16(1):380. doi: 10.1038/s41467-024-55340-5.
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.
人类癌细胞系是癌症研究的支柱。最近的报告显示，高度突变的成人癌细胞系（主要是HeLa和MCF-7）在不同实验室之间存在显著差异，长期连续培养会导致基因组/转录组异质性，并产生强烈的表型影响。在此，我们假设主要由融合转录因子驱动的低突变儿童肉瘤细胞系，如尤因肉瘤（EwS），在遗传和表型上比先前研究的成人癌细胞系更稳定。对多个EwS细胞系菌株进行全面的分子和表型特征分析，并在连续12个月的细胞培养过程中同时进行分析，结果表明，融合驱动的儿童肉瘤细胞系菌株在基因组上比成人癌菌株更稳定，表现出显著稳定且均匀的转录组，并呈现出一致且稳定的药物反应。此外，对多个经过长期连续培养的EwS细胞系的分析表明，融合驱动的细胞系之间存在不同程度的基因组/转录组/表型变化，进一步说明即使在同一肿瘤实体中，体外科学结果的可重复性潜力也可能被理解为一个范围。
