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Target sequencing and CRISPR/Cas editing reveal simultaneous loss of UTX and UTY in urothelial bladder cancer

Title
Target sequencing and CRISPR/Cas editing reveal simultaneous loss of UTX and UTY in urothelial bladder cancer
Authors
Ahn, JinwooKim, Kwang HyunPark, SanghuiAhn, Young-HoKim, Ha YoungYoon, HanaLee, Ji HyunBang, DuheeLee, Dong Hyeon
Ewha Authors
이동현윤하나박상희안영호김광현
SCOPUS Author ID
이동현scopus; 윤하나scopus; 박상희scopus; 안영호scopus; 김광현scopusscopus
Issue Date
2016
Journal Title
ONCOTARGET
ISSN
1949-2553JCR Link
Citation
ONCOTARGET vol. 7, no. 39, pp. 63252 - 63260
Keywords
urinary bladder neoplasmchromatin remodelingUTXUTYepigenesis
Publisher
IMPACT JOURNALS LLC
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
UTX is a histone demethylase gene located on the X chromosome and is a frequently mutated gene in urothelial bladder cancer (UBC). UTY is a paralog of UTX located on the Y chromosome. We performed target capture sequencing on 128 genes in 40 non-metastatic UBC patients. UTX was the most frequently mutated gene (30%, 12/40). Of the genetic alterations identified, 75% were truncating mutations. UTY copy number loss was detected in 8 male patients (22.8%, 8/35). Of the 9 male patients with UTX mutations, 6 also had copy number loss (66.7%). To evaluate the functional roles of UTX and UTY in tumor progression, we designed UTX and UTY single knockout and UTX-UTY double knockout experiments using a CRISPR/Cas9 lentiviral system, and compared the proliferative capacities of two UBC cell lines in vitro. Single UTX or UTY knockout increased cell proliferation as compared to UTX-UTY wild-type cells. UTX-UTY double knockout cells exhibited greater proliferation than single knockout cells. These findings suggest both UTX and UTY function as dose-dependent suppressors of UBC development. While UTX escapes X chromosome inactivation in females, UTY may function as a male homologue of UTX, which could compensate for dosage imbalances.
DOI
10.18632/oncotarget.11207
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의과대학 > 의학과 > Journal papers
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