Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy

• Published in: eLife Vol. 7
• Main Authors: Springer, Simeon U, Chen, Chung-Hsin, Rodriguez Pena, Maria Del Carmen, Li, Lu, Douville, Christopher, Wang, Yuxuan, Cohen, Joshua David, Taheri, Diana, Silliman, Natalie, Schaefer, Joy, Ptak, Janine, Dobbyn, Lisa, Papoli, Maria, Kinde, Isaac, Afsari, Bahman, Tregnago, Aline C, Bezerra, Stephania M, VandenBussche, Christopher, Fujita, Kazutoshi, Ertoy, Dilek, Cunha, Isabela W, Yu, Lijia, Bivalacqua, Trinity J, Grollman, Arthur P, Diaz, Luis A, Karchin, Rachel, Danilova, Ludmila, Huang, Chao-Yuan, Shun, Chia-Tung, Turesky, Robert J, Yun, Byeong Hwa, Rosenquist, Thomas A, Pu, Yeong-Shiau, Hruban, Ralph H, Tomasetti, Cristian, Papadopoulos, Nickolas, Kinzler, Ken W, Vogelstein, Bert, Dickman, Kathleen G, Netto, George J
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 20.03.2018; eLife Sciences Publications, Ltd
• Subjects: Aneuploidy; Aristolochia; bladder; Bladder cancer; cancer; Cancer Biology; Cellular biology; Copy number; Cytology; Deoxyribonucleic acid; DNA; DNA sequencing; FDA approval; Genes; Genomes; liquid biopsy; Medicine; Mutation; Pathology; Public health; renal pelvis; Toxicology; Tumors; ureter; Urine; Urology; Urothelial cancer; United States > US; Taipei Taiwan; Baltimore Maryland; Taiwan; ureter; genes; urine; bladder; chromosomes; renal pelvis; cancer; cancer biology; human; liquid biopsy
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.32143

Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer.