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 chrom...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/32143 |
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doaj-035e9fc0aa4749039ab3ee51913706ab |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy eLife liquid biopsy cancer urine bladder renal pelvis ureter |
| author_facet |
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 |
| author_sort |
Simeon U Springer |
| title |
Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy |
| title_short |
Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy |
| title_full |
Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy |
| title_fullStr |
Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy |
| title_full_unstemmed |
Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy |
| title_sort |
non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2018-03-01 |
| description |
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. |
| topic |
liquid biopsy cancer urine bladder renal pelvis ureter |
| url |
https://elifesciences.org/articles/32143 |
| work_keys_str_mv |
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doaj-035e9fc0aa4749039ab3ee51913706ab2021-05-05T15:44:27ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.32143Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidySimeon U Springer0https://orcid.org/0000-0002-2891-2111Chung-Hsin Chen1Maria Del Carmen Rodriguez Pena2https://orcid.org/0000-0002-3439-7013Lu Li3https://orcid.org/0000-0002-1920-4965Christopher Douville4https://orcid.org/0000-0002-2510-4151Yuxuan Wang5https://orcid.org/0000-0002-2932-6042Joshua David Cohen6https://orcid.org/0000-0003-1158-5668Diana Taheri7Natalie Silliman8Joy Schaefer9Janine Ptak10Lisa Dobbyn11Maria Papoli12Isaac Kinde13Bahman Afsari14Aline C Tregnago15Stephania M Bezerra16Christopher VandenBussche17Kazutoshi Fujita18Dilek Ertoy19Isabela W Cunha20Lijia Yu21https://orcid.org/0000-0001-6735-9569Trinity J Bivalacqua22Arthur P Grollman23Luis A Diaz24Rachel Karchin25Ludmila Danilova26Chao-Yuan Huang27Chia-Tung Shun28Robert J Turesky29Byeong Hwa Yun30Thomas A Rosenquist31Yeong-Shiau Pu32Ralph H Hruban33Cristian Tomasetti34Nickolas Papadopoulos35Ken W Kinzler36Bert Vogelstein37https://orcid.org/0000-0003-0766-3854Kathleen G Dickman38https://orcid.org/0000-0003-1308-2992George J Netto39https://orcid.org/0000-0003-3915-9134Howard Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesDepartment of Urology, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pathology, Johns Hopkins University, Baltimore, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, United StatesDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, United StatesDepartment of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesDepartment of Pathology, Johns Hopkins University, Baltimore, United States; Department of Pathology, Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, IranHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesDepartment 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 StatesDepartment of Pathology, Johns Hopkins University, Baltimore, United StatesDepartment of Pathology, AC Camargo Cancer Center, Sao Paulo, BrazilDepartment of Pathology, Johns Hopkins University, Baltimore, United StatesDepartment of Pathology, Osaka University, Osaka, JapanDepartment of Pathology, Hacettepe University, Ankara, TurkeyDepartment of Pathology, AC Camargo Cancer Center, Sao Paulo, BrazilDepartment of Pathology, University of Alabama at Birmingham, Birmingham, United StatesDepartment of Urology, Johns Hopkins University, Baltimore, United StatesDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, United States; Department of Medicine, Stony Brook University, Stony Brook, United StatesDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, United States; Department of Oncology, Johns Hopkins University, Baltimore, United StatesDivision 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, TurkeyDepartment of Urology, National Taiwan University Hospital, Taipei, TaiwanDepartment of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, TaiwanMasonic Cancer Center, University of Minnesota, Minneapolis, United States; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, United StatesMasonic Cancer Center, University of Minnesota, Minneapolis, United States; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, United StatesDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, United StatesDepartment of Urology, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pathology, Johns Hopkins University, Baltimore, United StatesDepartment 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 StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesHoward Hughes Medical Institute, Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, United States; Sidney Kimmel Comprehensive Cancer Center, Baltimore, United StatesDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, United States; Department of Medicine, Stony Brook University, Stony Brook, United StatesDepartment of Pathology, Johns Hopkins University, Baltimore, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, United StatesCurrent 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.https://elifesciences.org/articles/32143liquid biopsycancerurinebladderrenal pelvisureter |