eLife (Mar 2018)
Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy
- Simeon U Springer,
- Chung-Hsin Chen,
- Maria Del Carmen Rodriguez Pena,
- Lu Li,
- Christopher Douville,
- Yuxuan Wang,
- Joshua David Cohen,
- Diana Taheri,
- Natalie Silliman,
- Joy Schaefer,
- Janine Ptak,
- Lisa Dobbyn,
- Maria Papoli,
- Isaac Kinde,
- Bahman Afsari,
- Aline C Tregnago,
- Stephania M Bezerra,
- Christopher VandenBussche,
- Kazutoshi Fujita,
- Dilek Ertoy,
- Isabela W Cunha,
- Lijia Yu,
- Trinity J Bivalacqua,
- Arthur P Grollman,
- Luis A Diaz,
- Rachel Karchin,
- Ludmila Danilova,
- Chao-Yuan Huang,
- Chia-Tung Shun,
- Robert J Turesky,
- Byeong Hwa Yun,
- Thomas A Rosenquist,
- Yeong-Shiau Pu,
- Ralph H Hruban,
- Cristian Tomasetti,
- Nickolas Papadopoulos,
- Ken W Kinzler,
- Bert Vogelstein,
- Kathleen G Dickman,
- George J Netto
Affiliations
- Simeon U Springer
- ORCiD
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Chung-Hsin Chen
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
- Maria Del Carmen Rodriguez Pena
- ORCiD
- Department of Pathology, Johns Hopkins University, Baltimore, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, United States
- Lu Li
- ORCiD
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States
- Christopher Douville
- ORCiD
- Department of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, United States
- Yuxuan Wang
- ORCiD
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Joshua David Cohen
- ORCiD
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Diana Taheri
- Department of Pathology, Johns Hopkins University, Baltimore, United States; Department of Pathology, Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Natalie Silliman
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Joy Schaefer
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Janine Ptak
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Lisa Dobbyn
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Maria Papoli
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Isaac Kinde
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Bahman Afsari
- Department of Oncology, Johns Hopkins University, Baltimore, United States; Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, United States
- Aline C Tregnago
- Department of Pathology, Johns Hopkins University, Baltimore, United States
- Stephania M Bezerra
- Department of Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil
- Christopher VandenBussche
- Department of Pathology, Johns Hopkins University, Baltimore, United States
- Kazutoshi Fujita
- Department of Pathology, Osaka University, Osaka, Japan
- Dilek Ertoy
- Department of Pathology, Hacettepe University, Ankara, Turkey
- Isabela W Cunha
- Department of Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil
- Lijia Yu
- ORCiD
- Department of Pathology, University of Alabama at Birmingham, Birmingham, United States
- Trinity J Bivalacqua
- Department of Urology, Johns Hopkins University, Baltimore, United States
- Arthur P Grollman
- Department of Pharmacological Sciences, Stony Brook University, Stony Brook, United States; Department of Medicine, Stony Brook University, Stony Brook, United States
- Luis A Diaz
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States
- Rachel Karchin
- Department of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, United States; Department of Oncology, Johns Hopkins University, Baltimore, United States
- Ludmila Danilova
- Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, United States; Department of Pathology, Hacettepe University, Ankara, Turkey
- Chao-Yuan Huang
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
- Chia-Tung Shun
- Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan
- Robert J Turesky
- Masonic Cancer Center, University of Minnesota, Minneapolis, United States; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, United States
- Byeong Hwa Yun
- Masonic Cancer Center, University of Minnesota, Minneapolis, United States; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, United States
- Thomas A Rosenquist
- Department of Pharmacological Sciences, Stony Brook University, Stony Brook, United States
- Yeong-Shiau Pu
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
- Ralph H Hruban
- Department of Pathology, Johns Hopkins University, Baltimore, United States
- Cristian Tomasetti
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States; Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, United States
- Nickolas Papadopoulos
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Ken W Kinzler
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Bert Vogelstein
- ORCiD
- Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States
- Kathleen G Dickman
- ORCiD
- Department of Pharmacological Sciences, Stony Brook University, Stony Brook, United States; Department of Medicine, Stony Brook University, Stony Brook, United States
- George J Netto
- ORCiD
- Department of Pathology, Johns Hopkins University, Baltimore, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, United States
- DOI
- https://doi.org/10.7554/eLife.32143
- Journal volume & issue
-
Vol. 7
Abstract
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.
Keywords
