Methodology, criteria, and characterization of patient-matched thyroid cell lines and patient-derived tumor xenografts Journal Article


Authors: Marlow, L. A.; Rohl, S. D.; Miller, J. L.; Knauf, J. A.; Fagin, J. A.; Ryder, M.; Milosevic, D.; Netzel, B. C.; Grebe, S. K.; Reddi, H. V.; Smallridge, R. C.; Copland, J. A.
Article Title: Methodology, criteria, and characterization of patient-matched thyroid cell lines and patient-derived tumor xenografts
Abstract: Objective: To investigate the molecular underpinnings of thyroid cancer, preclinical cell line models are crucial; however, ;40% of these have been proven to be either duplicates of existing thyroid lines or even nonthyroid-derived lines or are not derived from humans at all. Therefore, we set out to establish procedures and guidelines that should proactively avoid these problems, which facilitated the creation of criteria to make valid preclinical models for thyroid cancer research. Design: Based on our recommendations, we systematically characterized all new cell lines that we generated by a standardized approach that included (1) determination of human origin, (2) exclusion of lymphoma, (3) DNA fingerprinting and histological comparisons to establish linkage to presumed tissue of origin, (4) examining thyroid differentiation by screening two to three thyroid markers, (5) examination of biological behavior (growth rate, tumorigenicity), and (6) presence of common thyroid cancer genetic changes (TP53, BRAF, PTEN, PIK3CA, RAS, TERT promoter, RET/PTC, PAX8/PPARg, NF1, and EIF1AX). Results: We established seven new thyroid cell lines (LAM136, EAM306, SDAR1, SDAR2, JEM493, THJ529, and THJ560) out of 294 primary culture attempts, and 10 patient-derived tumor xenografts (PDTXs; MC-Th-95, MC-Th-374, MC-Th-467, MC-Th-491, MC-Th-493, MC-Th-504, MC-Th-524, MC-Th- 529, MC-Th-560, and MC-Th-562) out of 67 attempts. All were successfully validated by our protocols. Conclusions: This standardized approach for cell line and PDTX characterization should prevent (or detect) future cross-contamination and ensure that only valid preclinical models are used for thyroid cancer research. © 2018 Endocrine Society.
Journal Title: Journal of Clinical Endocrinology and Metabolism
Volume: 103
Issue: 9
ISSN: 0021-972X
Publisher: Oxford University Press  
Date Published: 2018-09-01
Start Page: 3169
End Page: 3182
Language: English
DOI: 10.1210/jc.2017-01845
PROVIDER: scopus
PMCID: PMC6126888
PUBMED: 29846633
DOI/URL:
Notes: Article -- Export Date: 1 November 2018 -- Source: Scopus
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  1. James A Fagin
    180 Fagin
  2. Jeffrey A Knauf
    61 Knauf