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Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues

Patient-derived xenograft (PDX) models are useful tools for tumor biology research and testing the efficacy of candidate anticancer drugs targeting the druggable mutations identified in tumor tissue. However, it is still unknown how much of the genetic alterations identified in primary tumors are co...

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Autores principales: Yu, Sang Mi, Jung, Seung-Hyun, Chung, Yeun-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korea Genome Organization 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187809/
https://www.ncbi.nlm.nih.gov/pubmed/30304923
http://dx.doi.org/10.5808/GI.2018.16.2.30
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author Yu, Sang Mi
Jung, Seung-Hyun
Chung, Yeun-Jun
author_facet Yu, Sang Mi
Jung, Seung-Hyun
Chung, Yeun-Jun
author_sort Yu, Sang Mi
collection PubMed
description Patient-derived xenograft (PDX) models are useful tools for tumor biology research and testing the efficacy of candidate anticancer drugs targeting the druggable mutations identified in tumor tissue. However, it is still unknown how much of the genetic alterations identified in primary tumors are consistently detected in tumor tissues in the PDX model. In this study, we analyzed the genetic alterations of three primary colorectal cancers (CRCs) and matched xenograft tissues in PDX models using a next-generation sequencing cancer panel. Of the 17 somatic mutations identified from the three CRCs, 14 (82.4%) were consistently identified in both primary and xenograft tumors. The other three mutations identified in the primary tumor were not detected in the xenograft tumor tissue. There was no newly identified mutation in the xenograft tumor tissues. In addition to the somatic mutations, the copy number alteration profiles were also largely consistent between the primary tumor and xenograft tissue. All of these data suggest that the PDX tumor model preserves the majority of the key mutations detected in the primary tumor site. This study provides evidence that the PDX model is useful for testing targeted therapies in the clinical field and research on precision medicine.
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spelling pubmed-61878092018-10-17 Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues Yu, Sang Mi Jung, Seung-Hyun Chung, Yeun-Jun Genomics Inform Original Article Patient-derived xenograft (PDX) models are useful tools for tumor biology research and testing the efficacy of candidate anticancer drugs targeting the druggable mutations identified in tumor tissue. However, it is still unknown how much of the genetic alterations identified in primary tumors are consistently detected in tumor tissues in the PDX model. In this study, we analyzed the genetic alterations of three primary colorectal cancers (CRCs) and matched xenograft tissues in PDX models using a next-generation sequencing cancer panel. Of the 17 somatic mutations identified from the three CRCs, 14 (82.4%) were consistently identified in both primary and xenograft tumors. The other three mutations identified in the primary tumor were not detected in the xenograft tumor tissue. There was no newly identified mutation in the xenograft tumor tissues. In addition to the somatic mutations, the copy number alteration profiles were also largely consistent between the primary tumor and xenograft tissue. All of these data suggest that the PDX tumor model preserves the majority of the key mutations detected in the primary tumor site. This study provides evidence that the PDX model is useful for testing targeted therapies in the clinical field and research on precision medicine. Korea Genome Organization 2018-06 2018-06-30 /pmc/articles/PMC6187809/ /pubmed/30304923 http://dx.doi.org/10.5808/GI.2018.16.2.30 Text en Copyright © 2018 by the Korea Genome Organization It is identical to the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).
spellingShingle Original Article
Yu, Sang Mi
Jung, Seung-Hyun
Chung, Yeun-Jun
Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues
title Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues
title_full Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues
title_fullStr Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues
title_full_unstemmed Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues
title_short Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues
title_sort comparison of the genetic alterations between primary colorectal cancers and their corresponding patient-derived xenograft tissues
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187809/
https://www.ncbi.nlm.nih.gov/pubmed/30304923
http://dx.doi.org/10.5808/GI.2018.16.2.30
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