TY  - JOUR
AU  - Kasan, Merve
AU  - Geyer, Florian
AU  - Siebenlist, Jana
AU  - Sill, Martin
AU  - Öllinger, Rupert
AU  - Faehling, Tobias
AU  - de Álava, Enrique
AU  - Surdez, Didier
AU  - Dirksen, Uta
AU  - Oehme, Ina
AU  - Scotlandi, Katia
AU  - Delattre, Olivier
AU  - Müller-Nurasyid, Martina
AU  - Rad, Roland
AU  - Strauch, Konstantin
AU  - Grünewald, Thomas
AU  - Cidre-Aranaz, Florencia
TI  - Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2025-00063
SP  - 380
PY  - 2025
N1  - #EA:B410#LA:B410#
AB  - 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.
KW  - Humans
KW  - Sarcoma, Ewing: genetics
KW  - Sarcoma, Ewing: pathology
KW  - Cell Line, Tumor
KW  - Phenotype
KW  - Oncogene Proteins, Fusion: genetics
KW  - Oncogene Proteins, Fusion: metabolism
KW  - RNA-Binding Protein EWS: genetics
KW  - RNA-Binding Protein EWS: metabolism
KW  - Transcriptome
KW  - Gene Expression Regulation, Neoplastic
KW  - Child
KW  - Genomic Instability: genetics
KW  - Genomics: methods
KW  - Sarcoma: genetics
KW  - Sarcoma: pathology
KW  - Mutation
KW  - Oncogene Proteins, Fusion (NLM Chemicals)
KW  - RNA-Binding Protein EWS (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39753532
C2  - pmc:PMC11699042
DO  - DOI:10.1038/s41467-024-55340-5
UR  - https://inrepo02.dkfz.de/record/296133
ER  -