@article{a2f98fe056d84555a4c2446f331be33a,
title = "Detection and surveillance of bladder cancer using urine tumor DNA",
abstract = "Current regimens for the detection and surveillance of bladder cancer are invasive and have suboptimal sensitivity. Here, we present a novel high-throughput sequencing (HTS) method for detection of urine tumor DNA (utDNA) called utDNA CAPP-Seq (uCAPP-Seq) and apply it to 67 healthy adults and 118 patients with early-stage bladder cancer who had urine collected either prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per patient with bladder cancer and observed surprisingly frequent mutations of the PLEKHS1 promoter (46%), suggesting these mutations represent a useful biomarker for detection of bladder cancer. We detected utDNA pretreatment in 93% of cases using a tumor mutation-informed approach and in 84% when blinded to tumor mutation status, with 96% to 100% specifi city. In the surveillance setting, we detected utDNA in 91% of patients who ultimately recurred, with utDNA detection preceding clinical progression in 92% of cases. uCAPP-Seq outperformed a commonly used ancillary test (UroVysion, P = 0.02) and cytology and cystoscopy combined (P ≤ 0.006), detecting 100% of bladder cancer cases detected by cytology and 82% that cytology missed. Our results indicate that uCAPP-Seq is a promising approach for early detection and surveillance of bladder cancer.",
author = "Dudley, {Jonathan C.} and Joseph Schroers-Martin and Lazzareschi, {Daniel V.} and Shi, {William Y.} and Chen, {Simon B.} and Esfahani, {Mohammad S.} and Dharati Trivedi and Chabon, {Jacob J.} and Chaudhuri, {Aadel A.} and Henning Stehr and Liu, {Chih Long} and Harumi Lim and Costa, {Helio A.} and Nabet, {Barzin Y.} and Liao, {Joseph C.} and Alizadeh, {Ash A.} and Alizadeh, {Ash A.}",
note = "Funding Information: We are grateful to the patients and families involved in this study and to the Stanford Cytopathology laboratory for preserving samples for this study. This work was supported with grants from the Joint Initiative for Metrology in Biology (J. Dudley and M. Diehn; 1186777-204-SBARL), the Stanford Pathology Department (J. Dudley and M. Diehn; 1194947-105-DHCRE), the Stanford Cancer Institute (J. Schroers-Martin), Albert Institute for Bladder Cancer Care and Research (J. Liao and M. Diehn), the National Cancer Institute (M. Diehn and A. Alizadeh; R01CA188298), the U.S. National Institutes of Health Director{\textquoteright}s New Innovator Award Program (M. Diehn; 1-DP2-CA186569), the Virginia and D.K. Ludwig Fund for Cancer Research (M. Diehn and A. Alizadeh), and the CRK Faculty Scholar Fund (M. Diehn). This work used the Genome Sequencing Service Center by the Stanford Center for Genomics and Personalized Medicine, supported by the grant award NIH S10OD020141. Funding sources played no role in the writing of this manuscript or the decision to submit it for publication. Publisher Copyright: {\textcopyright} 2019 American Association for Cancer Research.",
year = "2019",
month = apr,
doi = "10.1158/2159-8290.CD-18-0825",
language = "English",
volume = "9",
pages = "500--509",
journal = "Cancer discovery",
issn = "2159-8274",
number = "4",
}