Regulatory region mutations of TERT, PLEKHS1 and GPR126 genes as urinary biomarkers in upper tract urothelial carcinomas

Xing, Xiangling; Yuan, Xiaotian; Liu, Tiantian; Dai, Mingkai; Fan, Yidong; Liu, Cheng; Strååt, Klas; Björkholm, Magnus; Xu, Dawei

doi:10.7150/jca.56779

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J Cancer 2021; 12(13):3853-3861. doi:10.7150/jca.56779 This issue Cite

Research Paper

Regulatory region mutations of TERT, PLEKHS1 and GPR126 genes as urinary biomarkers in upper tract urothelial carcinomas

Xiangling Xing¹, Xiaotian Yuan¹, Tiantian Liu^2✉, Mingkai Dai³, Yidong Fan⁴, Cheng Liu⁵, Klas Strååt¹, Magnus Björkholm¹, Dawei Xu¹

1. Department of Medicine, Division of Hematology, Bioclinicum and Center for Molecular Medicine (CMM), Karolinsk Institutet and Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden.
2. Pathology Department, School of Basic Medical Science, Shandong University, Jinan, PR China.
3. Central Research Laboratory, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, PR China.
4. Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China.
5. Department of Urology, Peking University Third Hospital, Beijing, PR China.

Citation:

Xing X, Yuan X, Liu T, Dai M, Fan Y, Liu C, Strååt K, Björkholm M, Xu D. Regulatory region mutations of TERT, PLEKHS1 and GPR126 genes as urinary biomarkers in upper tract urothelial carcinomas. J Cancer 2021; 12(13):3853-3861. doi:10.7150/jca.56779. https://www.jcancer.org/v12p3853.htm

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Abstract

Background: The hotspot regulatory region mutations of the TERT, PLEKHS1 and GPR126 genes have been shown to occur frequently in urothelial bladder carcinoma (UBC). However, it is currently unclear whether these mutations are all present in upper tract urothelial carcinomas (UTUC) including renal pelvic carcinoma (RPC) and ureter carcinoma (UC), although TERT promoter mutations were previously observed in these malignancies.

Methods: The hotspot mutations of TERT and PLEKHS1 promoters and GPR126 intron 6 (enhancer) in tumors derived from 164 patients with UTUC were determined using Sanger sequencing, and the obtained results were further compared with the mutation frequency in 106 UBCs. The mutations were also assessed in urine from patients with UTUC and UBC.

Results: The mutation frequencies in UTUC tumors were 28%, 5.8% and 11% for TERT and PLEKHS1 promoters and GPR126 intron 6, respectively, which were lower than those (44.3%, 26.4%, and 31.4%, respectively) in UBCs. The total frequencies for the presence of any of these mutations were 50.8% and 34.4% for RPCs and UCs, respectively. All these mutated DNA sequences were detectable in urine from both UTUC and UBC patients and disappeared rapidly in most patients after surgery.

Conclusions: This proof-of-concept study demonstrates that the hotspot mutations in the TERT, PLEKHS1 and GPR126 non-coding regions are present in UTUCs, and that urinary assays of these mutated sequences serve as potential biomarkers for UTUC diagnostics and disease monitoring.

Keywords: GPR126, PLEKHS1, TERT, Urinary biomarker, UBC, UTUC

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APA

Xing, X., Yuan, X., Liu, T., Dai, M., Fan, Y., Liu, C., Strååt, K., Björkholm, M., Xu, D. (2021). Regulatory region mutations of TERT, PLEKHS1 and GPR126 genes as urinary biomarkers in upper tract urothelial carcinomas. Journal of Cancer, 12(13), 3853-3861. https://doi.org/10.7150/jca.56779.

ACS

Xing, X.; Yuan, X.; Liu, T.; Dai, M.; Fan, Y.; Liu, C.; Strååt, K.; Björkholm, M.; Xu, D. Regulatory region mutations of TERT, PLEKHS1 and GPR126 genes as urinary biomarkers in upper tract urothelial carcinomas. J. Cancer 2021, 12 (13), 3853-3861. DOI: 10.7150/jca.56779.

NLM

CSE

Xing X, Yuan X, Liu T, Dai M, Fan Y, Liu C, Strååt K, Björkholm M, Xu D. 2021. Regulatory region mutations of TERT, PLEKHS1 and GPR126 genes as urinary biomarkers in upper tract urothelial carcinomas. J Cancer. 12(13):3853-3861.

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