A Single Nucleotide Polymorphism Genotyping Platform for the Authentication of Patient Derived Xenografts

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Aug 17

PMID 27528024

Citations 16

Authors

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

Richard B Lock

Affiliations

Soon will be listed here.

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.

Citing Articles

STRprofiler: efficient comparisons of short tandem repeat profiles for biomedical model authentication.

Andrews J, Lloyd M, Neuhauser S, Bundy M, Jocoy E, Airhart S Bioinformatics. 2024; 40(12).

PMID: 39589865 PMC: 11634538. DOI: 10.1093/bioinformatics/btae713.

PU.1 eviction at lymphocyte-specific chromatin domains mediates glucocorticoid response in acute lymphoblastic leukemia.

Beck D, Cao H, Tian F, Huang Y, Jiang M, Zhao H Nat Commun. 2024; 15(1):9697.

PMID: 39516193 PMC: 11549222. DOI: 10.1038/s41467-024-54096-2.

Challenges and Prospects of Patient-Derived Xenografts for Cancer Research.

Jin J, Yoshimura K, Sewastjanow-Silva M, Song S, Ajani J Cancers (Basel). 2023; 15(17).

PMID: 37686627 PMC: 10486659. DOI: 10.3390/cancers15174352.

A new intronic quantitative PCR method led to the discovery of transformation from human ascites to murine malignancy in a mouse model.

Jin J, Huo L, Fan Y, Wang R, Scott A, Pizzi M Front Oncol. 2023; 13:1062424.

PMID: 36865791 PMC: 9972586. DOI: 10.3389/fonc.2023.1062424.

The Molecular Subtype of Adult Acute Lymphoblastic Leukemia Samples Determines the Engraftment Site and Proliferation Kinetics in Patient-Derived Xenograft Models.

Richter A, Roolf C, Sekora A, Knuebel G, Krohn S, Lange S Cells. 2022; 11(1).

PMID: 35011712 PMC: 8750004. DOI: 10.3390/cells11010150.

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