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

Ashley Cornett, Harleen K. Athwal, Emily Hill, George Murphy, Kenji Yeoh, Christopher A. Moskaluk, Robert L. Witt, Nisha J. D'Silva, Seema Agarwal, Isabelle M.A. Lombaert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)175-184
Number of pages10
JournaleBioMedicine
Volume41
DOIs
StatePublished - Mar 2019
Externally publishedYes

Keywords

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

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