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Cited by 3Molecular Biology Techniques and ApplicationsCancer Genomics and DiagnosticsIdentification and Quantification in Food

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

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Jin, Jiankang, Huo, Longfei, Fan, Yibo, Wang, Ruiping, Scott, Ailing W., Pizzi, Melissa Pool, Yao, Xiaodan, Shao, Shan +9 more·2023·Frontiers in Oncology
DOI 10.3389/fonc.2023.1062424PMC PMC9972586
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Abstract

Purpose: To establish a fast and accurate detection method for interspecies contaminations in the patient-derived xenograft (PDX) models and cell lines, and to elucidate possible mechanisms if interspecies oncogenic transformation is detected. Methods: A fast and highly sensitive intronic qPCR method detecting Gapdh intronic genomic copies was developed to quantify if cells were human or murine or a mixture. By this method, we documented that murine stromal cells were abundant in the PDXs; we also authenticated our cell lines to be human or murine. Results: In one mouse model, GA0825-PDX transformed murine stromal cells into a malignant tumorigenic murine P0825 cell line. We traced the timeline of this transformation and discovered three subpopulations descended from the same GA0825-PDX model: epithelium-like human H0825, fibroblast-like murine M0825, and main passaged murine P0825 displayed differences in tumorigenic capability in vivo . P0825 was the most aggressive and H0825 was weakly tumorigenic. Immunofluorescence (IF) staining revealed that P0825 cells highly expressed several oncogenic and cancer stem cell markers. Whole exosome sequencing (WES) analysis revealed that TP53 mutation in the human ascites IP116-generated GA0825-PDX may have played a role in the human-to-murine oncogenic transformation. Conclusion: This intronic qPCR is able to quantify human/mouse genomic copies with high sensitivity and within a time frame of a few hours. We are the first to use intronic genomic qPCR for authentication and quantification of biosamples. Human ascites transformed murine stroma into malignancy in a PDX model.

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  • In workflows involving admixtures such as patient-derived xenografts where human tumor cells grow in mouse stroma, dPCR can detect human DNA in a murine background.

    “In workflows involving admixtures, such as patient-derived xenografts where human tumor cells grow in mouse stroma, dPCR can detect human DNA in a murine background [57].”

    From Genetic Insights into the Economic Toll of Cell Line Misidentification: A Comprehensive Review (2026) · cites this paper as [57]

    The Results section (page unavailable) reports detection of human and mouse genomic DNA in mixed samples, including PDX tumors. But the method tested is intronic quantitative PCR (qPCR), not digital PCR (dPCR), so the cited paper does not establish the claim about dPCR. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Jin, J., Huo, L., Fan, Y., Wang, R., Scott, A. W., Pizzi, M. P., Yao, X., Shao, S., Ma, L., Da Silva, M. S., Yamashita, K., Yoshimura, K., Zhang, B., Wu, J., Wang, L., Song, S., & Ajani, J. A.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
  • Jin, Jiankang
  • Song, Shumei
  • Ajani, Jaffer A.
ORCID
Venue
Frontiers in Oncology
Publisher
Frontiers Media SA
Published
2023-02-06
Volume
13
Pages
1062424-1062424
ISSN
2234-943X (ISSN-L)
DOI
10.3389/fonc.2023.1062424
PMC
PMC9972586
OpenAlex
W4319322420
Cited by
3
References
1
Citations by year
2026: 1 · 2024: 1 · 2023: 1
FWCI
0.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Defense (CA170906, CA200990, CA160433, CA160445)
  • Strong
  • Gastric Cancer Foundation
  • National Institutes of Health
  • National Cancer Institute (R01CA138671, R01CA160433, R21CA129906, R01CA172741)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Identification and Quantification in Food
Keywords
patient-derived xenografts, oncogenic transformation, cell line authentication, TP53 mutation, cancer stem cell markers, tumorigenicity, mouse model

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