Abstract 3418: A NGS-based SNP array for the identification of human xenograft tumors, mouse homograft tumors, human and mouse cell lines, organoids
Authors: Xiaobo Chen, Wubin Qian, Sheng Guo, Henry Li
Journal: Cancer Research (2019)

Abstract Transplanted tumor models, including xenograft tumors (e.g. patient derived xenograft, or PDX, human cell line derived tumors, mouse homograft (e.g. syngeneic tumors), as well as many cancer cell lines of both human and mouse origins are the key preclinical tools used in cancer researches, including drug efficacy assessment, drug target/biomarker discovery, as well as drug mechanism of actions and resistances, etc. The broad applications of these models in all different global laboratories at different times creates great risk of cross-contaminations (intra-/inter-species) as well as unintended de-identification. It is prudent to be able to track and QC tumors to ensure their authenticity by a simple and routine assays. The most common assay to identify human xenografts are Short Tandem Repeat (STR) test using multiple independently assorted STR loci. However, STR testing may suffer from several limitations, e.g. inadequate accuracy, especially for samples of kinship or close genetic background, inability to distinguish tumor of mouse origins as well as assessing mouse components in human xenografts. In addition, STR is also labor intensive, costly, low through-put, and ineffective for samples of low amount/poor quality. Single Nucleotide Polymorphisms (SNPs) based assays are increasingly used recently to replace STR testing with higher accuracy1-4. SNPs are genetic markers at single-nucleotide resolution. It is also amicable to automation, suitable for low amount/degraded samples with fragment length as short as only 60-80bp. Multiple SNPs can be simultaneously assayed by Next Generation Sequencing (NGS) technology. We developed a NGS-based SNP array for the identification of our libraries of xenografts, homografts, cell lines, etc. The assay is consisted of ~300 SNPs, 200 of which are used to authenticate different human origins, which were first constructed as unique fingerprints for every PDX from Whole-Exome Sequencing (WES) and RNAseq data, followed by that a sample is tested by the NGS-based SNP array to obtain its SNP fingerprint which is compared against all known fingerprints. The remaining 100 SNPs are used to infer gender and ethnicity, common viral infection, mouse content, mouse strain, homograft tumors, etc., as well as possible mycoplasmas contamination. Validation studies on multiple PDX models show that the array achieves near perfect results. In summary, we have established a high-throughput multi-purpose NGS-based SNP array that can be applied to the quality assurance of all the common cancer models. Citation Format: Xiaobo Chen, Wubin Qian, Sheng Guo, Henry Li. A NGS-based SNP array for the identification of human xenograft tumors, mouse homograft tumors, human and mouse cell lines, organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3418.