Oncotarget

Research Papers:

A single nucleotide polymorphism genotyping platform for the authentication of patient derived xenografts

Jad El-Hoss, Duohui Jing, Kathryn Evans, Cara Toscan, Jinhan Xie, Hyunjoo Lee, Renea A. Taylor, Mitchell G. Lawrence, Gail P. Risbridger, Karen L. MacKenzie, Rosemary Sutton and Richard B. Lock _

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Oncotarget. 2016; 7:60475-60490. https://doi.org/10.18632/oncotarget.11125

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Abstract

Jad El-Hoss1,*, Duohui Jing1,*, Kathryn Evans1, Cara Toscan1, Jinhan Xie1, Hyunjoo Lee1, Renea A. Taylor2, Mitchell G. Lawrence3, Gail P. Risbridger3, Karen L. MacKenzie1, Rosemary Sutton1, Richard B. Lock1

1Children’s Cancer Institute, Lowy Cancer Research Centre, Sydney, UNSW, Australia

2Prostate Research Group, Department of Physiology, Biomedicine Discovery Institute, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, VIC, Australia

3Prostate Research Group, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, VIC, Australia

*These authors have contributed equally to this work

Correspondence to:

Richard B. Lock, email: rlock@ccia.unsw.edu.au

Keywords: SNP genotyping, patient derived xenografts, authentication, OpenArray, R studio

Received: December 06, 2015    Accepted: July 26, 2016    Published: August 09, 2016

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.


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