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
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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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