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 & 20 others Isabela W. Cunha, Lijia Yu, Trinity Bivalacqua, Arthur P. Grollman, Luis A. Diaz, Rachel Karchin, Liudmila V 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, Kenneth W Kinzler, Bert Vogelstein, Kathleen G. Dickman, George J. Netto

Research output: Contribution to journalArticle

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

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Cytology
Aneuploidy
Urinary Bladder Neoplasms
Genes
Cell Biology
Neoplasm DNA
Mutation
Neoplasms
Urine
Chromosomes
Gene Dosage
Tumors
Assays
Recurrence

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Springer, S. U., Chen, C. H., Del Carmen Rodriguez Pena, M., Li, L., Douville, C., Wang, Y., ... Netto, G. J. (2018). Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. eLife, 7, [e32143]. https://doi.org/10.7554/eLife.32143

Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. / Springer, Simeon U.; Chen, Chung Hsin; Del Carmen Rodriguez Pena, Maria; 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; Grollman, Arthur P.; Diaz, Luis A.; Karchin, Rachel; Danilova, Liudmila V; 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, Kenneth W; Vogelstein, Bert; Dickman, Kathleen G.; Netto, George J.

In: eLife, Vol. 7, e32143, 20.03.2018.

Research output: Contribution to journalArticle

Springer, SU, Chen, CH, Del Carmen Rodriguez Pena, M, Li, L, Douville, C, Wang, Y, Cohen, JD, Taheri, D, Silliman, N, Schaefer, J, Ptak, J, Dobbyn, L, Papoli, M, Kinde, I, Afsari, B, Tregnago, AC, Bezerra, SM, VandenBussche, C, Fujita, K, Ertoy, D, Cunha, IW, Yu, L, Bivalacqua, T, Grollman, AP, Diaz, LA, Karchin, R, Danilova, LV, Huang, CY, Shun, CT, Turesky, RJ, Yun, BH, Rosenquist, TA, Pu, YS, Hruban, RH, Tomasetti, C, Papadopoulos, N, Kinzler, KW, Vogelstein, B, Dickman, KG & Netto, GJ 2018, 'Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy', eLife, vol. 7, e32143. https://doi.org/10.7554/eLife.32143
Springer SU, Chen CH, Del Carmen Rodriguez Pena M, Li L, Douville C, Wang Y et al. Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. eLife. 2018 Mar 20;7. e32143. https://doi.org/10.7554/eLife.32143
Springer, Simeon U. ; Chen, Chung Hsin ; Del Carmen Rodriguez Pena, Maria ; 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 ; Grollman, Arthur P. ; Diaz, Luis A. ; Karchin, Rachel ; Danilova, Liudmila V ; 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, Kenneth W ; Vogelstein, Bert ; Dickman, Kathleen G. ; Netto, George J. / Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. In: eLife. 2018 ; Vol. 7.
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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.",
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T1 - Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy

AU - Springer, Simeon U.

AU - Chen, Chung Hsin

AU - Del Carmen Rodriguez Pena, Maria

AU - Li, Lu

AU - Douville, Christopher

AU - Wang, Yuxuan

AU - Cohen, Joshua David

AU - Taheri, Diana

AU - Silliman, Natalie

AU - Schaefer, Joy

AU - Ptak, Janine

AU - Dobbyn, Lisa

AU - Papoli, Maria

AU - Kinde, Isaac

AU - Afsari, Bahman

AU - Tregnago, Aline C.

AU - Bezerra, Stephania M.

AU - VandenBussche, Christopher

AU - Fujita, Kazutoshi

AU - Ertoy, Dilek

AU - Cunha, Isabela W.

AU - Yu, Lijia

AU - Bivalacqua, Trinity

AU - Grollman, Arthur P.

AU - Diaz, Luis A.

AU - Karchin, Rachel

AU - Danilova, Liudmila V

AU - Huang, Chao Yuan

AU - Shun, Chia Tung

AU - Turesky, Robert J.

AU - Yun, Byeong Hwa

AU - Rosenquist, Thomas A.

AU - Pu, Yeong Shiau

AU - Hruban, Ralph H

AU - Tomasetti, Cristian

AU - Papadopoulos, Nickolas

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - Dickman, Kathleen G.

AU - Netto, George J.

PY - 2018/3/20

Y1 - 2018/3/20

N2 - 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.

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