Dataset Information
Novel Anaplastic Thyroid Cancer PDXs and Cell Lines: Expanding Preclinical Models of Genetic Diversity.
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ABSTRACT: Context
Anaplastic thyroid cancer (ATC) is a rare, aggressive, and deadly disease. Robust preclinical thyroid cancer models are needed to adequately develop and study novel therapeutic agents. Patient-derived xenograft (PDX) models may resemble patient tumors by recapitulating key genetic alterations and gene expression patterns, making them excellent preclinical models for drug response evaluation.Objective
We developed distinct ATC PDX models concurrently with cell lines and characterized them in vitro and in vivo.Methods
Fresh thyroid tumor from patients with a preoperative diagnosis of ATC was surgically collected and divided for concurrent cell line and PDX model development. Cell lines were created by generating single cells through enzymatic digestion. PDX models were developed following direct subcutaneous implantation of fresh tumor on the flank of immune compromised/athymic mice.Results
Six ATC PDX models and 4 cell lines were developed with distinct genetic profiles. Mutational characterization showed one BRAF/TP53/CDKN2A, one BRAF/CDKN2A, one BRAF/TP53, one TP53 only, one TERT-promoter/HRAS, and one TERT-promoter/KRAS/TP53/NF2/NFE2L2 mutated phenotype. Hematoxylin-eosin staining comparing the PDX models to the original patient surgical specimens show remarkable resemblance, while immunohistochemistry stains for important biomarkers were in full concordance (cytokeratin, TTF-1, PAX8, BRAF). Short tandem repeats DNA fingerprinting analysis of all PDX models and cell lines showed strong concordance with the original tumor. PDX successful establishment rate was 32%.Conclusion
We have developed and characterized 6 novel ATC PDX models with 4 matching cell lines. Each PDX model harbors a distinct genetic profile, making them excellent tools for preclinical therapeutic trials.
SUBMITTER: Maniakas A
PROVIDER: S-EPMC8530744 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Novel Anaplastic Thyroid Cancer PDXs and Cell Lines: Expanding Preclinical Models of Genetic Diversity.
The Journal of clinical endocrinology and metabolism 20211001 11
<h4>Context</h4>Anaplastic thyroid cancer (ATC) is a rare, aggressive, and deadly disease. Robust preclinical thyroid cancer models are needed to adequately develop and study novel therapeutic agents. Patient-derived xenograft (PDX) models may resemble patient tumors by recapitulating key genetic alterations and gene expression patterns, making them excellent preclinical models for drug response evaluation.<h4>Objective</h4>We developed distinct ATC PDX models concurrently with cell lines and ch ...[more]
