Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models
Patient-derived xenograft (PDX) models, which can retain the characteristics of original tumors in an in vivo-mimicking environment, have been developed to identify better treatment options. However, although original tumors and xenograft tissues mostly share oncogenic mutations and global gene expr...
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| Format: | Article |
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MDPI AG
2023-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/11/2934 |
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| author | Hyeongsun Jeong Hyo Eun Moon Seongmin Yun Seung Woo Cho Hye Ran Park Sung-Hye Park Kyungjae Myung Taejoon Kwon Sun Ha Paek |
| author_facet | Hyeongsun Jeong Hyo Eun Moon Seongmin Yun Seung Woo Cho Hye Ran Park Sung-Hye Park Kyungjae Myung Taejoon Kwon Sun Ha Paek |
| author_sort | Hyeongsun Jeong |
| collection | DOAJ |
| description | Patient-derived xenograft (PDX) models, which can retain the characteristics of original tumors in an in vivo-mimicking environment, have been developed to identify better treatment options. However, although original tumors and xenograft tissues mostly share oncogenic mutations and global gene expression patterns, their detailed mutation profiles occasionally do not overlap, indicating that selection occurs in the xenograft environment. To understand this mutational alteration in xenografts, we established 13 PDX models derived from 11 brain tumor patients and confirmed their histopathological similarity. Surprisingly, only a limited number of somatic mutations were shared between the original tumor and xenograft tissue. By analyzing deleteriously mutated genes in tumors and xenografts, we found that previously reported brain tumor-related genes were enriched in PDX samples, demonstrating that xenografts are a valuable platform for studying brain tumors. Furthermore, mutated genes involved in cilium movement, microtubule depolymerization, and histone methylation were enriched in PDX samples compared with the original tumors. Even with the limitations of the heterogeneity of clinical lesions with a heterotropic model, our study demonstrates that PDX models can provide more information in genetic analysis using samples with high heterogeneity, such as brain tumors. |
| first_indexed | 2024-03-09T17:00:20Z |
| format | Article |
| id | doaj.art-2fb4e78106194fff8c21c55c3f3c5263 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T17:00:20Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-2fb4e78106194fff8c21c55c3f3c52632023-11-24T14:30:48ZengMDPI AGBiomedicines2227-90592023-10-011111293410.3390/biomedicines11112934Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft ModelsHyeongsun Jeong0Hyo Eun Moon1Seongmin Yun2Seung Woo Cho3Hye Ran Park4Sung-Hye Park5Kyungjae Myung6Taejoon Kwon7Sun Ha Paek8Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaDepartment of Neurosurgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaDepartment of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaDepartment of Neurosurgery, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of KoreaDepartment of Pathology, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaDepartment of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaDepartment of Neurosurgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaPatient-derived xenograft (PDX) models, which can retain the characteristics of original tumors in an in vivo-mimicking environment, have been developed to identify better treatment options. However, although original tumors and xenograft tissues mostly share oncogenic mutations and global gene expression patterns, their detailed mutation profiles occasionally do not overlap, indicating that selection occurs in the xenograft environment. To understand this mutational alteration in xenografts, we established 13 PDX models derived from 11 brain tumor patients and confirmed their histopathological similarity. Surprisingly, only a limited number of somatic mutations were shared between the original tumor and xenograft tissue. By analyzing deleteriously mutated genes in tumors and xenografts, we found that previously reported brain tumor-related genes were enriched in PDX samples, demonstrating that xenografts are a valuable platform for studying brain tumors. Furthermore, mutated genes involved in cilium movement, microtubule depolymerization, and histone methylation were enriched in PDX samples compared with the original tumors. Even with the limitations of the heterogeneity of clinical lesions with a heterotropic model, our study demonstrates that PDX models can provide more information in genetic analysis using samples with high heterogeneity, such as brain tumors.https://www.mdpi.com/2227-9059/11/11/2934patient-derived xenograft (PDX)somatic mutationshistone modificationciliogenesisbrain tumor |
| spellingShingle | Hyeongsun Jeong Hyo Eun Moon Seongmin Yun Seung Woo Cho Hye Ran Park Sung-Hye Park Kyungjae Myung Taejoon Kwon Sun Ha Paek Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models Biomedicines patient-derived xenograft (PDX) somatic mutations histone modification ciliogenesis brain tumor |
| title | Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models |
| title_full | Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models |
| title_fullStr | Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models |
| title_full_unstemmed | Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models |
| title_short | Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models |
| title_sort | enrichment of deleterious mutated genes involved in ciliary function and histone modification in brain cancer patient derived xenograft models |
| topic | patient-derived xenograft (PDX) somatic mutations histone modification ciliogenesis brain tumor |
| url | https://www.mdpi.com/2227-9059/11/11/2934 |
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