Oral Cavity Squamous Cell Carcinoma Xenografts Retain Complex Genotypes and Intertumor Molecular Heterogeneity

Katie M. Campbell, Tianxiang Lin, Paul Zolkind, Erica K. Barnell, Zachary L. Skidmore, Ashley E. Winkler, Jonathan H. Law, Elaine R. Mardis, Lukas D. Wartman, Douglas R. Adkins, Rebecca D. Chernock, Malachi Griffith, Ravindra Uppaluri, Obi L. Griffith

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Herein, we report an oral cavity squamous cell carcinoma (OCSCC) patient-derived xenograft (PDX) platform, with genomic annotation useful for co-clinical trial and mechanistic studies. Genomic analysis included whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) on 16 tumors and matched PDXs and additional whole-genome sequencing (WGS) on 9 of these pairs as a representative subset of a larger OCSCC PDX repository (n = 63). In 12 models with high purity, more than 90% of variants detected in the tumor were retained in the matched PDX. The genomic landscape across these PDXs reflected OCSCC molecular heterogeneity, including previously described basal, mesenchymal, and classical molecular subtypes. To demonstrate the integration of PDXs into a clinical trial framework, we show that pharmacological intervention in PDXs parallels clinical response and extends patient data. Together, these data describe a repository of OCSCC-specific PDXs and illustrate conservation of primary tumor genotypes, intratumoral heterogeneity, and co-clinical trial application. Campbell et al. report the genomic fidelity of patient-derived xenograft models from oral cavity squamous cell carcinomas. These models conserve the mutation and expression profile of their matched tumors, validating their use for co-clinical trial and mechanistic studies.

Original languageEnglish
Pages (from-to)2167-2178
Number of pages12
JournalCell Reports
Volume24
Issue number8
DOIs
StatePublished - Aug 21 2018

Keywords

  • genomic conservation
  • oral cavity squamous cell carcinoma
  • xenografts

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