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Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution.

ABSTRACT: Our findings reveal a high degree of both genomic and transcriptomic heterogeneity in established and globally utilized PDAC cell lines, custodial variation induced by growing apparently identical PDAC cell lines in different laboratories, and profound transcriptomic shifts in transitioning from 2D to 3D spheroid growth models. Our findings also call into question the validity of widely available immortalized, non-transformed pancreatic lines as contemporaneous “control” lines in experiments. Further, while patient-derived organoids (PDOs) are known to reflect the cognate in vivo biology of the parental tumor, we identify transcriptomic shifts during ex vivo passage that might hamper their predictive abilities over time. The impact of these findings on rigor and reproducibility of experimental data generated using established preclinical PDAC models between and across laboratories is uncertain, but a matter of concern.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173339 | GEO | 2022/04/28

REPOSITORIES: GEO

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