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. 2012 Jun 27:4:33-40.
doi: 10.2147/RRU.S32736. eCollection 2012.

Detection of low frequency FGFR3 mutations in the urine of bladder cancer patients using next-generation deep sequencing

John M Millholland  1 , Shuqiang Li, Cecilia A Fernandez, Anthony P Shuber
Affiliations

Detection of low frequency FGFR3 mutations in the urine of bladder cancer patients using next-generation deep sequencing

John M Millholland et al. Res Rep Urol. .

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] Res Rep Urol. 2012 Sep 12;4:47. doi: 10.2147/RRU.S36425. eCollection 2012. Res Rep Urol. 2012. PMID: 24199180 Free PMC article.

Abstract

Biological fluid-based noninvasive biomarker assays for monitoring and diagnosing disease are clinically powerful. A major technical hurdle for developing these assays is the requirement of high analytical sensitivity so that biomarkers present at very low levels can be consistently detected. In the case of biological fluid-based cancer diagnostic assays, sensitivities similar to those of tissue-based assays are difficult to achieve with DNA markers due to the high abundance of normal DNA background present in the sample. Here we describe a new urine-based assay that uses ultradeep sequencing technology to detect single mutant molecules of fibroblast growth factor receptor 3 (FGFR3) DNA that are indicative of bladder cancer. Detection of FGFR3 mutations in urine would provide clinicians with a noninvasive means of diagnosing early-stage bladder cancer. The single-molecule assay detects FGFR3 mutant DNA when present at as low as 0.02% of total urine DNA and results in 91% concordance with the frequency that FGFR3 mutations are detected in bladder cancer tumors, significantly improving diagnostic performance. To our knowledge, this is the first practical application of next-generation sequencing technology for noninvasive cancer diagnostics.

Keywords: FGFR3; bladder cancer; mutation; sequencing; single molecule; urine.

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References

    1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–236. - PubMed
    1. Billerey C, Chopin D, Aubriot-Lorton MH, et al. Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol. 2001;158(6):1955–1959. - PMC - PubMed
    1. Cappellen D, De Oliveira C, Ricol D, et al. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet. 1999;23(1):18–20. - PubMed
    1. van Rhijn BW, Lurkin I, Radvanyi F, Kirkels WJ, van der Kwast TH, Zwarthoff EC. The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res. 2001;61(4):1265–1268. - PubMed
    1. van Rhijn BW, Vis AN, van der Kwast TH, et al. Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome. J Clin Oncol. 2003;21(10):1912–1921. - PubMed