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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BioMed Central
2020-03-01
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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. |
format | Article |
id | doaj-art-2ddc18643a0945a8853b2162e4819541 |
institution | Kabale University |
issn | 2234-0742 |
language | English |
publishDate | 2020-03-01 |
publisher | BioMed Central |
record_format | Article |
series | Genomics & Informatics |
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 |
work_keys_str_mv | AT jaewonkim validityofpatientderivedxenograftmousemodelsforlungcancerbasedonexomesequencingdata AT hwanseokrhee validityofpatientderivedxenograftmousemodelsforlungcancerbasedonexomesequencingdata AT jhingookkim validityofpatientderivedxenograftmousemodelsforlungcancerbasedonexomesequencingdata AT sanghyuklee validityofpatientderivedxenograftmousemodelsforlungcancerbasedonexomesequencingdata |