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Cell Rep. 2018 Aug 21;24(8):2167-2178. doi: 10.1016/j.celrep.2018.07.058.

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

Author information

1
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.
2
Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63108, USA.
3
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
4
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
5
Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
6
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63108, USA.
7
Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Surgery/Otolaryngology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: ravindra_uppaluri@dfci.harvard.edu.
8
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108, USA. Electronic address: obigriffith@wustl.edu.

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.

KEYWORDS:

genomic conservation; oral cavity squamous cell carcinoma; xenografts

PMID:
30134176
DOI:
10.1016/j.celrep.2018.07.058
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