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EBioMedicine. 2019 Mar;41:175-184. doi: 10.1016/j.ebiom.2019.02.011. Epub 2019 Feb 11.

Serial patient-derived orthotopic xenografting of adenoid cystic carcinomas recapitulates stable expression of phenotypic alterations and innervation.

Author information

1
University of Michigan, Biointerfaces Institute, Ann Arbor, MI, United States; University of Michigan, School of Dentistry, Department of Biologic and Materials Sciences, Ann Arbor, MI, United States.
2
University of Virginia, School of Medicine, Department of Pathology, Charlottesville, VA, United States.
3
Thomas Jefferson University, Department of Otolaryngology-Head and Neck Surgery, Philadelphia, PA, United States.
4
University of Michigan, School of Dentistry, Department of Periodontics and Oral Medicine, Ann Arbor, MI, United States; University of Michigan, Medical School, Department of Pathology, Ann Arbor, MI, United States.
5
Georgetown University Medical Center, Department of Pathology, Center for Cell Reprogramming, Washington, DC, United States.
6
University of Michigan, Biointerfaces Institute, Ann Arbor, MI, United States; University of Michigan, School of Dentistry, Department of Biologic and Materials Sciences, Ann Arbor, MI, United States. Electronic address: lombaert@umich.edu.

Abstract

BACKGROUND:

Patient-derived xenograft (PDX) models have significantly enhanced cancer research, and often serve as a robust model. However, enhanced growth rate and altered pathological phenotype with serial passages have repeatedly been shown in adenoid cystic carcinoma (ACC) PDX tumors, which is a major concern.

METHODS:

We evaluated the fidelity of ACCs in their natural habitat by performing ACC orthotopic xenotransplantation (PDOX) in salivary glands.

FINDINGS:

Our PDOX model enabled solid tumors to integrate within the local epithelial, stromal and neuronal environment. Over serial passages, PDOX tumors maintained their stereotypic MYB-NFIB translocation, and FGFR2 and ATM point mutations. Tumor growth rate and histopathology were retained, including ACCs hallmark presentations of cribriform, tubular, solid areas and innervation. We also demonstrate that the PDOX model retains its capacity as a tool for drug testing.

INTERPRETATION:

Unlike the precedent PDX model, our data shows that the PDOX is a superior model for future cancer biology and therapy research. FUND: This work was supported by the National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) grants DE022557, DE027034, and DE027551.

KEYWORDS:

Adenoid cystic carcinoma; Drug treatment; Fidelity; Neural invasion; Orthotopic PDX model; Salivary gland

PMID:
30765319
PMCID:
PMC6442226
DOI:
10.1016/j.ebiom.2019.02.011
[Indexed for MEDLINE]
Free PMC Article

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