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

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.
Competing Interests: SS, CC, MR, LL, CD, YW, JC, DT, NS, JS, JP, LD, MP, IK, BA, AT, SB, CV, KF, DE, IC, LY, TB, AG, LD, RK, LD, CH, CS, RT, BY, TR, YP, RH, CT, KD, GN No competing interests declared, NP Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies. Luis A Diaz: Member of the board of directors of Personal Genome Diagnostics (PGDx) and Jounce Therapeutics. LAD holds equity in PapGene, Personal Genome Diagnostics (PGDx) and Phoremost. He is a paid consultant for Merck, PGDx and Phoremost. LAD is an inventor of licensed intellectual property related to technology for ctDNA analyses and mismatch repair deficiency for diagnosis and therapy from Johns Hopkins University. These licenses and relationships are associated with equity or royalty payments to LAD. The terms of all these arrangements are being managed by Johns Hopkins and Memorial Sloan Kettering in accordance with their conflict of interest policies. In addition, in the past 5 years, LAD has participated as a paid consultant for one-time engagements with Caris, Lyndra, Genocea Biosciences, Illumina and Cell Design Labs. KK Ken W Kinzler: Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies. BV Bert Vogelstein: Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies.
(© 2018, Springer et al.)