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 ErtoyIsabela 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

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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.

Original languageEnglish (US)
Article numbere32143
JournaleLife
Volume7
DOIs
StatePublished - Mar 20 2018

Bibliographical note

Funding Information:
This research was supported by grants from the National Science Council, Taiwan to CHC (104– 2314-B-002–132) and to YSP (104–2314-B-002–121-MY3). We appreciate the clinical services provided by Dr. Kuo-How Huang, Shuo-Meng Wang, Huai-Ching Tai and Yuan-Ju Lee (Department of Urology, National Taiwan University Hospital). We are grateful for the generous support provided by Henry and Marsha Laufer, the Virginia and DK Ludwig Fund for Cancer Research, the Commonwealth Foundation, the John Templeton Foundation, and the Conrad R Hilton Foundation. All sequencing was performed at the Sol Goldman Sequencing Facility at Johns Hopkins. This work was also supported by grants from the NIH (Grants CA-77598, CA 06973, GM 07309, and ES019564). The authors appreciate the medical illustrations skillfully designed by Kathleen Gebhart (Media Services, Stony Brook University). The authors appreciate the help in editing by Janice Nigro. National Science Council 104-2314-B-002-132 Chung-Hsin Chen Yeong-Shiau Pu National Science Council 104-2314-B-002-121-MY3 Chung-Hsin Chen Yeong-Shiau Pu National Institutes of Health Yuxuan Wang Arthur P Grollman Ken W Kinzler Henry and Marsha Laufer Arthur P Grollman John Templeton Foundation Cristian Tomasetti Conrad N. Hilton Foundation Nickolas Papadopoulos Ludwig Institute for Cancer Research Ken W Kinzler Bert Vogelstein Sol Goldman Pancreatic Research Foundation Bert Vogelstein The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Funding Information:
This research was supported by grants from the National Science Council, Taiwan to CHC (104– 2314-B-002–132) and to YSP (104–2314-B-002–121-MY3). We appreciate the clinical services provided by Dr. Kuo-How Huang, Shuo-Meng Wang, Huai-Ching Tai and Yuan-Ju Lee (Department of Urology, National Taiwan University Hospital). We are grateful for the generous support provided by Henry and Marsha Laufer, the Virginia and DK Ludwig Fund for Cancer Research, the Commonwealth Foundation, the John Templeton Foundation, and the Conrad R Hilton Foundation. All sequencing was performed at the Sol Goldman Sequencing Facility at Johns Hopkins. This work was also supported by grants from the NIH (Grants CA-77598, CA 06973, GM 07309, and ES019564). The authors appreciate the medical illustrations skillfully designed by Kathleen Gebhart (Media Services, Stony Brook University). The authors appreciate the help in editing by Janice Nigro.

Publisher Copyright:
© Springer et al.

Fingerprint Dive into the research topics of 'Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy'. Together they form a unique fingerprint.

Cite this