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Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models

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Title
Enrichment of Deleterious Mutated Genes Involved in Ciliary Function and Histone Modification in Brain Cancer Patient-Derived Xenograft Models
Author(s)
Hyeongsun Jeong; Moon, Hyo Eun; Yun, Seongmin; Seung Woo Cho; Park, Hye Ran; Park, Sung-Hye; Kyungjae Myung; Taejoon Kwon; Paek, Sun Ha
Publication Date
2023-11
Journal
BIOMEDICINES, v.11, no.11
Publisher
MDPI
Abstract
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.
URI
https://pr.ibs.re.kr/handle/8788114/14393
DOI
10.3390/biomedicines11112934
ISSN
2227-9059
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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