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http://dx.doi.org/10.5808/GI.2020.18.1.e3

Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data  

Kim, Jaewon (Department of Bio-information Science, Ewha Womans University)
Rhee, Hwanseok (Bioinformatics Team, DNA Link)
Kim, Jhingook (Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Lee, Sanghyuk (Ewha Research Center for Systems Biology (ERCSB) and Department of Life Science, Ewha Womans University)
Publication Information
Genomics & Informatics / v.18, no.1, 2020 , pp. 3.1-3.8 More about this Journal
Abstract
Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.
Keywords
copy number alteration; lung neoplasms; mutation; patient-derived xenograft; whole exome sequencing;
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