title: A single nucleotide polymorphism genotyping platform for the authentication of patient derived xenografts.
abstract: Patient derived xenografts (PDXs) have become a vital, frequently used, component of anti-cancer drug development. PDXs can be serially passaged in vivo for years, and shared across laboratories. As a consequence, the potential for mis-identification and cross-contamination is possible, yet authentication of PDXs appears limited. We present a PDX Authentication System (PAS), by combining a commercially available OpenArray assay of single nucleotide polymorphisms (SNPs) with in-house R studio programs, to validate PDXs established in individual mice from acute lymphoblastic leukemia biopsies. The PAS is sufficiently robust to identify contamination at levels as low as 3%, similar to the gold standard of short tandem repeat (STR) profiling. We have surveyed a panel of PDXs established from 73 individual leukemia patients, and found that the PAS provided sufficient discriminatory power to identify each xenograft. The identified SNP-discrepant PDXs demonstrated distinct gene expression profiles, indicating a risk of contamination for PDXs at high passage number. The PAS also allows for the authentication of tumor cells with complex karyotypes from solid tumors including prostate cancer and Ewing's sarcoma. This study highlights the demands of authenticating PDXs for cancer research, and evaluates a reliable authentication platform that utilizes a commercially available and cost-effective system.
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Jad
authors.initials: J
authors.lastname: El-Hoss
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Duohui
authors.initials: D
authors.lastname: Jing
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Evans
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Cara
authors.initials: C
authors.lastname: Toscan
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Jinhan
authors.initials: J
authors.lastname: Xie
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Hyunjoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: Prostate Research Group, Department of Physiology, Biomedicine Discovery Institute, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, VIC, Australia.
authors.forename: Renea A
authors.initials: RA
authors.lastname: Taylor
authors.affiliation: Prostate Research Group, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, VIC, Australia.
authors.forename: Mitchell G
authors.initials: MG
authors.lastname: Lawrence
authors.affiliation: Prostate Research Group, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, VIC, Australia.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Risbridger
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Karen L
authors.initials: KL
authors.lastname: MacKenzie
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Sutton
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lock
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D046528:Chimerism; D002869:Chromosome Aberrations; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics*; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays
keywords: OpenArray; R studio; SNP genotyping; authentication; patient derived xenografts