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

El-Hoss, J; Jing, D; Evans, K; Toscan, C; Xie, J; Lee, H; Taylor, RA; Lawrence, MG; Risbridger, GP; MacKenzie, KL; Sutton, R; Lock, RB

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

El-Hoss, J Jing, D

Evans, K Toscan, C Xie, J Lee, H Taylor, RA Lawrence, MG Risbridger, GP MacKenzie, KL Sutton, R Lock, RB

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Publisher:: IMPACT JOURNALS LLC
Publication Type:: Journal Article
Citation:: Oncotarget, 2016, 7, (37), pp. 60475-60490
Issue Date:: 2016-09-13

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Field	Value	Language
dc.contributor.author	El-Hoss, J
dc.contributor.author	Jing, D https://orcid.org/0000-0002-1491-8002
dc.contributor.author	Evans, K
dc.contributor.author	Toscan, C
dc.contributor.author	Xie, J
dc.contributor.author	Lee, H
dc.contributor.author	Taylor, RA
dc.contributor.author	Lawrence, MG
dc.contributor.author	Risbridger, GP
dc.contributor.author	MacKenzie, KL
dc.contributor.author	Sutton, R
dc.contributor.author	Lock, RB
dc.date.accessioned	2022-08-20T07:35:29Z
dc.date.available	2016-07-26
dc.date.available	2022-08-20T07:35:29Z
dc.date.issued	2016-09-13
dc.identifier.citation	Oncotarget, 2016, 7, (37), pp. 60475-60490
dc.identifier.issn	1949-2553
dc.identifier.issn	1949-2553
dc.identifier.uri	http://hdl.handle.net/10453/160558
dc.description.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.
dc.format	Print
dc.language	eng
dc.publisher	IMPACT JOURNALS LLC
dc.relation.ispartof	Oncotarget
dc.relation.isbasedon	10.18632/oncotarget.11125
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1112 Oncology and Carcinogenesis
dc.subject.mesh	Animals
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Chimerism
dc.subject.mesh	Chromosome Aberrations
dc.subject.mesh	Female
dc.subject.mesh	Genotype
dc.subject.mesh	High-Throughput Nucleotide Sequencing
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Mice
dc.subject.mesh	Mice, SCID
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Precursor Cell Lymphoblastic Leukemia-Lymphoma
dc.subject.mesh	Prostatic Neoplasms
dc.subject.mesh	Sarcoma, Ewing
dc.subject.mesh	Tissue Array Analysis
dc.subject.mesh	Xenograft Model Antitumor Assays
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Mice, SCID
dc.subject.mesh	Prostatic Neoplasms
dc.subject.mesh	Chromosome Aberrations
dc.subject.mesh	Tissue Array Analysis
dc.subject.mesh	Xenograft Model Antitumor Assays
dc.subject.mesh	Genotype
dc.subject.mesh	Chimerism
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Precursor Cell Lymphoblastic Leukemia-Lymphoma
dc.subject.mesh	High-Throughput Nucleotide Sequencing
dc.subject.mesh	Sarcoma, Ewing
dc.title	A single nucleotide polymorphism genotyping platform for the authentication of patient derived xenografts.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	United States
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	closed_access	*
dc.date.updated	2022-08-20T07:35:22Z
pubs.issue	37
pubs.publication-status	Published
pubs.volume	7
utslib.citation.issue	37

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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http://hdl.handle.net/10453/160558