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

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 compari...

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Main Authors: Jaewon Kim, Hwanseok Rhee, Jhingook Kim, Sanghyuk Lee
Format: Article
Language:English
Published: BioMed Central 2020-03-01
Series:Genomics & Informatics
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Online Access:http://genominfo.org/upload/pdf/gi-2020-18-1-e3.pdf
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author Jaewon Kim
Hwanseok Rhee
Jhingook Kim
Sanghyuk Lee
author_facet Jaewon Kim
Hwanseok Rhee
Jhingook Kim
Sanghyuk Lee
author_sort Jaewon Kim
collection DOAJ
description 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.
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institution Kabale University
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spelling doaj-art-2ddc18643a0945a8853b2162e48195412025-02-02T15:12:18ZengBioMed CentralGenomics & Informatics2234-07422020-03-0118110.5808/GI.2020.18.1.e3594Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing dataJaewon Kim0Hwanseok Rhee1Jhingook Kim2Sanghyuk Lee3 Department of Bio-information Science, Ewha Womans University, Seoul 03760, Korea Bioinformatics Team, DNA Link, Seoul 03759, Korea Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea Ewha Research Center for Systems Biology (ERCSB) and Department of Life Science, Ewha Womans University, Seoul 03760, KoreaPatient-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.http://genominfo.org/upload/pdf/gi-2020-18-1-e3.pdfcopy number alterationlung neoplasmsmutationpatient-derived xenograftwhole exome sequencing
spellingShingle Jaewon Kim
Hwanseok Rhee
Jhingook Kim
Sanghyuk Lee
Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data
Genomics & Informatics
copy number alteration
lung neoplasms
mutation
patient-derived xenograft
whole exome sequencing
title Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data
title_full Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data
title_fullStr Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data
title_full_unstemmed Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data
title_short Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data
title_sort validity of patient derived xenograft mouse models for lung cancer based on exome sequencing data
topic copy number alteration
lung neoplasms
mutation
patient-derived xenograft
whole exome sequencing
url http://genominfo.org/upload/pdf/gi-2020-18-1-e3.pdf
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AT hwanseokrhee validityofpatientderivedxenograftmousemodelsforlungcancerbasedonexomesequencingdata
AT jhingookkim validityofpatientderivedxenograftmousemodelsforlungcancerbasedonexomesequencingdata
AT sanghyuklee validityofpatientderivedxenograftmousemodelsforlungcancerbasedonexomesequencingdata