Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer

被引：212

作者：

Birkenkamp-Demtroder, Karin ^{[1
]}

Nordentoft, Iver ^{[1
]}

Christensen, Emil ^{[1
]}

Hoyer, Soren ^{[2
]}

Reinert, Thomas ^{[1
]}

Vang, Soren ^{[1
]}

Borre, Michael ^{[3
]}

Agerbaek, Mads ^{[4
]}

Jensen, Jorgen Bjerggaard ^{[3
]}

Orntoft, Torben F. ^{[1
]}

Dyrskjot, Lars ^{[1
]}

机构：

[1] Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark

[2] Aarhus Univ Hosp, Dept Pathol, DK-8000 Aarhus C, Denmark

[3] Aarhus Univ Hosp, Dept Urol, DK-8000 Aarhus N, Denmark

[4] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus C, Denmark

来源：

EUROPEAN UROLOGY | 2016年 / 70卷 / 01期

关键词：

Biomarker; Cell-free DNA; Circulating DNA; Droplet digital PCR; Genomic variant; Next-generation sequencing; NMIBC; Personalised analysis; Plasma; Urine; CIRCULATING TUMOR DNA; UROTHELIAL CARCINOMA; SIGNATURES; GENES;

D O I：

10.1016/j.eururo.2016.01.007

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

100201 [内科学]; 100221 [泌尿外科学];

摘要：

Background: At least half of the patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) experience recurrence and approximately 15% will develop progression to muscle invasive or metastatic disease. Biomarkers for disease surveillance are urgently needed. Objective: Development of assays for surveillance using genomic variants in cell-free tumour DNA from plasma and urine. Design, setting, and participants: Retrospective pilot study of 377 samples from 12 patients with recurrent or progressive/metastatic disease. Three next-generation sequencing methods were applied and somatic variants in DNA from tumour, plasma, and urine were subsequently monitored by personalised assays using droplet digital polymerase chain reaction (ddPCR). Samples were collected from 1994 to 2015, with up to 20 yr of follow-up. Outcome measurements and statistical analysis: Progression to muscle-invasive or metastatic bladder cancer; t test for ddPCR data. Results and limitations: We developed from one to six personalised assays per patient. Patients with progressive disease showed significantly higher levels of tumour DNA in plasma and urine before disease progression, compared with patients with recurrent disease (p = 0.032 and 1.3 x 10(-6), respectively). Interestingly, tumour DNA was detected in plasma and urine in patients with noninvasive disease, being no longer detectable in disease-free patients. A significant level of heterogeneity was observed for each patient; this could be due to tumour heterogeneity or assay performance. Conclusions: Cell-free tumour DNA can be detected in plasma and urine, even in patients with noninvasive disease, with high levels of tumour DNA detectable before progression, especially in urine samples. Personalised assays of genomic variants may be useful for disease monitoring. Patient summary: Tumour DNA can be detected in blood and urine in early and advanced stages of bladder cancer. Measurement of these highly tumour-specific biomarkers may represent a novel diagnostic tool to indicate the presence of residual disease or to discover aggressive forms of bladder cancer early in the disease course. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

引用

页码：75 / 82

页数：8

共 31 条

[1]

Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[2]

EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2013 [J].

Babjuk, Marko ;

Burger, Maximilian ;

Zigeuner, Richard ;

Shariat, Shahrokh F. ;

van Rhijn, Bas W. G. ;

Comperat, Eva ;

Sylvester, Richard J. ;

Kaasinen, Eero ;

Boehle, Andreas ;

Palou Redorta, Joan ;

Roupret, Morgan .

EUROPEAN UROLOGY, 2013, 64 (04) :639-653

[3]

ARID1A Alterations Are Associated with FGFR3-Wild Type, Poor-Prognosis, Urothelial Bladder Tumors [J].

Balbas-Martinez, Cristina ;

Rodriguez-Pinilla, Maria ;

Casanova, Ariel ;

Dominguez, Orlando ;

Pisano, David G. ;

Gomez, Gonzalo ;

Lloreta, Josep ;

Lorente, Jose A. ;

Malats, Nuria ;

Real, Francisco X. .

PLOS ONE, 2013, 8 (05)

[4]

Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy [J].

Balbas-Martinez, Cristina ;

Sagrera, Ana ;

Carrillo-de-Santa-Pau, Enrique ;

Earl, Julie ;

Marquez, Mirari ;

Vazquez, Miguel ;

Lapi, Eleonora ;

Castro-Giner, Francesc ;

Beltran, Sergi ;

Bayes, Monica ;

Carrato, Alfredo ;

Cigudosa, Juan C. ;

Dominguez, Orlando ;

Gut, Marta ;

Herranz, Jesus ;

Juanpere, Nuria ;

Kogevinas, Manolis ;

Langa, Xavier ;

Lopez-Knowles, Elena ;

Lorente, Jose A. ;

Lloreta, Josep ;

Pisano, David G. ;

Richart, Laia ;

Rico, Daniel ;

Salgado, Rocio N. ;

Tardon, Adonina ;

Chanock, Stephen ;

Heath, Simon ;

Valencia, Alfonso ;

Losada, Ana ;

Gut, Ivo ;

Malats, Nuria ;

Real, Francisco X. .

NATURE GENETICS, 2013, 45 (12) :1464-U221

[5]

Baronzio G, 2012, ANTICANCER RES, V32, P405

[6]

Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[7]

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM [J].

Bryan, R. T. ;

Regan, H. L. ;

Pirrie, S. J. ;

Devall, A. J. ;

Cheng, K. K. ;

Zeegers, M. P. ;

James, N. D. ;

Knowles, M. A. ;

Ward, D. G. .

BRITISH JOURNAL OF CANCER, 2015, 112 (06) :1052-1058

[8]

Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR [J].

Dyrskjot, L. ;

Reinert, T. ;

Novoradovsky, A. ;

Zuiverloon, T. C. M. ;

Beukers, W. ;

Zwarthoff, E. ;

Malats, N. ;

Real, F. X. ;

Segersten, U. ;

Malmstrom, P-U ;

Knowles, M. ;

Hurst, C. ;

Sorge, J. ;

Borre, M. ;

Orntoft, T. F. .

BRITISH JOURNAL OF CANCER, 2012, 107 (08) :1392-1398

[9]

Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma:: A multicenter validation study [J].

Dyrskjot, Lars ;

Zieger, Karsten ;

Real, Francisco X. ;

Malats, Nuria ;

Carrato, Alfredo ;

Hurst, Carolyn ;

Kotwal, Sanjeev ;

Knowles, Margaret ;

Malmstrom, Per-Uno ;

de la Torre, Manuel ;

Wester, Kenneth ;

Allory, Yves ;

Vordos, Dirnitri ;

Caillault, Aurelie ;

Radvanyi, Francois ;

Hein, Anne-Mette K. ;

Jensen, Jens L. ;

Jensen, Klaus M. E. ;

Marcussen, Niels ;

Orntoft, Torben F. .

CLINICAL CANCER RESEARCH, 2007, 13 (12) :3545-3551

[10]

A census of human cancer genes [J].

Futreal, PA ;

Coin, L ;

Marshall, M ;

Down, T ;

Hubbard, T ;

Wooster, R ;

Rahman, N ;

Stratton, MR .

NATURE REVIEWS CANCER, 2004, 4 (03) :177-183

← 1 2 3 4 →