Oral Cavity Squamous Cell Carcinoma Xenografts Retain Complex Genotypes and Intertumor Molecular Heterogeneity
Year: 2018
Type: article
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.
Source: Cell Reports
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Cancer Research Foundation, Novartis, National Institutes of Health, National Cancer Institute, Cairo University, National Human Genome Research Institute, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research
Awards: G12431752, G1686905186, G2038818704, Development of Clinician/Researchers in Academic ENT, HISTONE H3 METHYLATION AND EPIGENOMICS IN ACUTE LEUKEMIA, G5310623310, G5682028659, G5841304809, DEFINING THE REGULATORY, NON-CODING, MUTATIONAL LANDSCAPE OF BREAST CANCER, G7085622784, G7187942286, Cancer Center Support Grant
OpenAlex ID: W2888083388