Detection of multiple mutations in urinary exfoliated cells from male bladder cancer patients at diagnosis and during follow-up
Metrics: PDF 1767 views | HTML 2867 views | ?
Rossana Critelli1, Francesca Fasanelli2, Marco Oderda3, Silvia Polidoro1, Manuela Bianca Assumma1, Clara Viberti2,4, Mirko Preto3, Paolo Gontero3, Giuseppina Cucchiarale5, Irene Lurkin6, Ellen C. Zwarthoff6, Paolo Vineis1,7, Carlotta Sacerdote8, Giuseppe Matullo2,4, Alessio Naccarati1
1Molecular and Genetic Epidemiology Unit, Human Genetics Foundation, Turin, Italy
2Department of Medical Sciences, University of Turin, Turin, Italy
3Department of Surgical Sciences, Urology, University of Turin, Turin, Italy
4Genomic Variation in Human Populations and Complex Diseases Unit, Human Genetics Foundation, Turin, Italy
5Department of Urology, Humanitas Cellini, Turin, Italy
6Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
7Department of Surgery and Cancer, Imperial College London, London, UK
8Unit of Cancer Epidemiology, Centre for Cancer Prevention (CPO-Piemonte), Turin, Italy
Alessio Naccarati, email: [email protected]
Keywords: bladder cancer, urine mutation analyses, TERT, recurrence
Received: May 27, 2016 Accepted: August 25, 2016 Published: September 07, 2016
Most bladder cancer (BC) patients need life-long, invasive and expensive monitoring and treatment, making it a serious burden on the health system. Thus, there is a pressing need for an accurate test to assist diagnosis and surveillance of BC as an alternative to cystoscopy. Mutations in human TERT, FGFR3, PIK3CA, and RAS genes have been proposed as potential molecular markers in bladder tumor. Their concomitant presence in urine samples has not been fully explored.
We investigated a panel of mutations in DNA from exfoliated urinary cells of 255 BC patients at diagnosis. Forty-one mutations in TERT, FGFR3, PIK3CA, and RAS were analyzed by SNaPshot assay in relation to clinical outcome. In 81 of these patients under surveillance, the same set of mutations was screened in additional 324 samples prospectively collected.
The most common mutations detected in urine at diagnosis were in the TERT promoter. In non-invasive BC, these mutations were related to high risk and grade (p<0.0001) as well as progression to muscle-invasive disease (p=0.01), whereas FGFR3 mutations were observed in low-grade BC (p=0.02) and patients with recurrences (p=0.05). Stronger associations were observed for combined TERT and FGFR3 mutations and number of recurrences (OR: 4.54 95% CI: 1.23-16.79, p=0.02). Analyses of the area under the curve for combinations of mutations detected at diagnosis and follow-up showed an accuracy of prediction of recurrence of 0.80 (95% CI: 0.71-0.89).
Mutations in urine of BC patients may represent reliable biomarkers. In particular, TERT and FGFR3 mutations have a good accuracy of recurrence prediction.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.