Oncotarget

Research Papers:

The genetic difference between Western and Chinese urothelial cell carcinomas: infrequent FGFR3 mutation in Han Chinese patients

Xiaotian Yuan, Cheng Liu, Kun Wang, Li Liu, Tiantian Liu, Nan Ge, Feng Kong, Liu Yang, Magnus Björkholm, Yidong Fan _, Shengtian Zhao and Dawei Xu

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Oncotarget. 2016; 7:25826-25835. https://doi.org/10.18632/oncotarget.8404

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Abstract

Xiaotian Yuan1,2,3,*, Cheng Liu4,*, Kun Wang2,3,4,*, Li Liu5, Tiantian Liu6, Nan Ge1, Feng Kong1, Liu Yang1, Magnus Björkholm2,3, Yidong Fan4, Shengtian Zhao1, Dawei Xu2,3

1Department of Central Research Laboratory and Urology, Shandong University Second Hospital, Jinan, China

2Department of Medicine, Division of Haematology and Centre for Molecular Medicine (CMM), Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden

3Karolinska Institutet-Shandong University Collaborative Laboratory for Cancer Research, Jinan, China

4Department of Urology, Shandong University Qilu Hospital, Jinan, China

5Shandong University Nursing School, Jinan, China

6Department of Pathology, Shandong University School of Medicine, Jinan, China

*These authors contributed equally to this work

Correspondence to:

Yidong Fan, e-mail: [email protected]

Shengtian Zhao, e-mail: [email protected]

Keywords: FGFR3 mutation, racial disparity, TERT promoter mutation, urothelial bladder carcinoma, upper track urothelial carcinoma

Received: January 25, 2016     Accepted: February 28, 2016     Published: March 26, 2016

ABSTRACT

Urothelial cell carcinoma (UCC) includes urothelial bladder carcinoma (UBC), renal pelvic carcinoma (RPC) and ureter carcinoma (UC), and its incidence varies dependent on geographical areas and tumor locations, which indicates different oncogenic mechanisms and/or different genetic susceptibility/environment exposure. The activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene and telomerase reverse transcriptase (TERT) promoter are the most frequent genetic events in UCCs. These mutations have clinical utilities in UCC initial diagnostics, prognosis, recurrence monitoring and management. However, the vast majority of the results are obtained from studies of UCC patients in Western countries, and little has been known about these in Han Chinese patients. In the present study, we screened the FGFR3 gene and TERT promoter for mutations in 116 UBC, 91 RPC and 115 UC tumors from Han Chinese patients by using Sanger Sequencing. TERT promoter mutations occurred at a high frequency in these UCC patients, comparable with that seen in Western patients, however, the FGFR3 mutation was surprisingly lower, only 9.4% for UBCs, 8.8% for RPCs and 2.6% for UCs, respectively. Taken together, the FGFR3 gene is an infrequent target in the pathogenesis of Han Chinese UCCs, and its mutation detection and targeted therapy have limited clinical utility in these patients. Our results underscore the need for extensive characterization of cancer genomes from diverse patient populations, thereby contributing to precision medicine for cancer treatment and prevention.


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