Oncotarget

Clinical Research Papers:

TERT promoter mutations are associated with distant metastases in upper tract urothelial carcinomas and serve as urinary biomarkers detected by a sensitive castPCR

Kun Wang _, Tiantian Liu, Nan Ge, Li Liu, Xiaotian Yuan, Jikai Liu, Feng Kong, Chang Wang, Hongbo Ren, Keqiang Yan, Sanyuan Hu, Zhonghua Xu, Magnus Björkholm, Yidong Fan, Shengtian Zhao, Cheng Liu and Dawei Xu

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Oncotarget. 2014; 5:12428-12439. https://doi.org/10.18632/oncotarget.2660

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Abstract

Kun Wang1,2,*, Tiantian Liu3,*, Nan Ge4,*, Li Liu5, Xiaotian Yuan2, Jikai Liu1, Feng Kong4, Chang Wang2, Hongbo Ren1, Keqiang Yan1, Sanyuan Hu6, Zhonghua Xu1, Magnus Björkholm2, Yidong Fan1, Shengtian Zhao4, Cheng Liu1, Dawei Xu2,4

1Department of Urology, Shandong University Qilu Hospital, Jinan, China

2Department of Medicine, Division of Hematology and Centre for Molecular Medicine, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden

3Department of Pathology, Shandong University School of Medicine, Jinan, China

4Department of Urology and Central Research Laboratory, Shandong University Second Hospital, Jinan, China

5Shandong University School of Nursing, Jinan, China

6Department of General Surgery, Shandong University Qilu Hospital, Jinan, China

*These authors contributed equally to this work

Correspondence to:

Shengtian Zhao, e-mail: [email protected]

Cheng Liu, e-mail: [email protected]

Keywords: Cancer biomarkers, Promoter mutations, Telomerase, TERT, UTUC

Received: September 02, 2014     Accepted: October 26, 2014     Published: December 09, 2014

ABSTRACT

TERT promoter C228T and C250T mutations occur in various malignancies including bladder cancer (BC) and may serve as urinary tumor markers. However, the mutation association with clinical variables in upper tract urothelial carcinomas (UTUCs) is unclear. There is also a lack of sensitive tools to detect the minor mutant TERT promoter in bulk urinary DNA. Here we analyzed 220 UTUC patients [98 with renal pelvic carcinoma (RPC) and 122 with ureter carcinoma (UC)] and developed a Competitive Allele-Specific TaqMan PCR (castPCR) for urinary assay. We identified C228T or C250T mutations in 42 of 98 (43%) RPC and 23 of 122 (19%) UC tumors. Distant metastases were significantly correlated with UTUC patients harboring TERT promoter mutations (P = 0.001). C228T were detected in 6/10 and 9/10 of urine samples from patients with mutation-carrying tumors using Sanger sequencing and castPCR, respectively. When urine samples from 70 BC patients were analyzed together, the sensitivity of urinary C228T assay was 89% and 50% for castPCR and Sanger sequencing, respectively (P < 0.001). Collectively, TERT promoter mutations occur in UTUCs with a high frequency in RPCs and predict distant metastasis. castPCR assays of the mutation are a useful tool for urine-based diagnostics of urological malignancies.


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