Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer

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Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer. / Birkenkamp-Demtröder, Karin; Nordentoft, Iver Kristiansen; Christensen, Emil; Høyer, Søren; Reinert, Thomas; Vang, Søren; Borre, Michael; Agerbæk, Mads; Jensen, Jørgen Bjerggaard; Ørntoft, Torben Falck; Dyrskjøt, Lars .

In: European Urology, 21.01.2016.

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@article{8ab75eb2580c4e48a3ba3181acf75061,
title = "Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer",
abstract = "Background: At least half of the patients diagnosed with non–muscle-invasive bladdercancer (NMIBC) experience recurrence and approximately 15{\%} will develop progression tomuscle invasive or metastatic disease. Biomarkers for disease surveillance are urgentlyneeded.Objective: Development of assays for surveillance using genomic variants in cell-freetumour DNA from plasma and urine.Design, setting, and participants: Retrospective pilot study of 377 samples from 12 patientswith recurrent or progressive/metastatic disease. Three next-generation sequencing methodswere applied and somatic variants in DNA from tumour, plasma, and urine weresubsequently monitored by personalised assays using droplet digital polymerase chainreaction (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 metastaticbladder 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 inplasma and urine before disease progression, compared with patients with recurrent disease(p = 0.032 and 1.3 106, respectively). Interestingly, tumour DNA was detected in plasmaand urine in patients with noninvasive disease, being no longer detectable in disease-freepatients. A significant level of heterogeneity was observed for each patient; this could be dueto tumour heterogeneity or assay performance.Conclusions: Cell-free tumour DNA can be detected in plasma and urine, even in patientswith noninvasive disease, with high levels of tumour DNA detectable before progression,especially in urine samples. Personalised assays of genomic variants may be useful fordisease monitoring.Patient summary: Tumour DNA can be detected in blood and urine in early and advancedstages of bladder cancer. Measurement of these highly tumour-specific biomarkers mayrepresent a novel diagnostic tool to indicate the presence of residual disease or to discoveraggressive forms of bladder cancer early in the disease course.",
keywords = "Biomarker; Cell-free DNA; Circulating DNA; Droplet digital PCR; Genomic variant; Next-generation sequencing; NMIBC; Personalised analysis; Plasma; Urine",
author = "Karin Birkenkamp-Demtr{\"o}der and Nordentoft, {Iver Kristiansen} and Emil Christensen and S{\o}ren H{\o}yer and Thomas Reinert and S{\o}ren Vang and Michael Borre and Mads Agerb{\ae}k and Jensen, {J{\o}rgen Bjerggaard} and {\O}rntoft, {Torben Falck} and Lars Dyrskj{\o}t",
year = "2016",
month = "1",
day = "21",
doi = "10.1016/j.eururo.2016.01.007",
language = "English",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer

AU - Birkenkamp-Demtröder, Karin

AU - Nordentoft, Iver Kristiansen

AU - Christensen, Emil

AU - Høyer, Søren

AU - Reinert, Thomas

AU - Vang, Søren

AU - Borre, Michael

AU - Agerbæk, Mads

AU - Jensen, Jørgen Bjerggaard

AU - Ørntoft, Torben Falck

AU - Dyrskjøt, Lars

PY - 2016/1/21

Y1 - 2016/1/21

N2 - Background: At least half of the patients diagnosed with non–muscle-invasive bladdercancer (NMIBC) experience recurrence and approximately 15% will develop progression tomuscle invasive or metastatic disease. Biomarkers for disease surveillance are urgentlyneeded.Objective: Development of assays for surveillance using genomic variants in cell-freetumour DNA from plasma and urine.Design, setting, and participants: Retrospective pilot study of 377 samples from 12 patientswith recurrent or progressive/metastatic disease. Three next-generation sequencing methodswere applied and somatic variants in DNA from tumour, plasma, and urine weresubsequently monitored by personalised assays using droplet digital polymerase chainreaction (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 metastaticbladder 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 inplasma and urine before disease progression, compared with patients with recurrent disease(p = 0.032 and 1.3 106, respectively). Interestingly, tumour DNA was detected in plasmaand urine in patients with noninvasive disease, being no longer detectable in disease-freepatients. A significant level of heterogeneity was observed for each patient; this could be dueto tumour heterogeneity or assay performance.Conclusions: Cell-free tumour DNA can be detected in plasma and urine, even in patientswith noninvasive disease, with high levels of tumour DNA detectable before progression,especially in urine samples. Personalised assays of genomic variants may be useful fordisease monitoring.Patient summary: Tumour DNA can be detected in blood and urine in early and advancedstages of bladder cancer. Measurement of these highly tumour-specific biomarkers mayrepresent a novel diagnostic tool to indicate the presence of residual disease or to discoveraggressive forms of bladder cancer early in the disease course.

AB - Background: At least half of the patients diagnosed with non–muscle-invasive bladdercancer (NMIBC) experience recurrence and approximately 15% will develop progression tomuscle invasive or metastatic disease. Biomarkers for disease surveillance are urgentlyneeded.Objective: Development of assays for surveillance using genomic variants in cell-freetumour DNA from plasma and urine.Design, setting, and participants: Retrospective pilot study of 377 samples from 12 patientswith recurrent or progressive/metastatic disease. Three next-generation sequencing methodswere applied and somatic variants in DNA from tumour, plasma, and urine weresubsequently monitored by personalised assays using droplet digital polymerase chainreaction (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 metastaticbladder 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 inplasma and urine before disease progression, compared with patients with recurrent disease(p = 0.032 and 1.3 106, respectively). Interestingly, tumour DNA was detected in plasmaand urine in patients with noninvasive disease, being no longer detectable in disease-freepatients. A significant level of heterogeneity was observed for each patient; this could be dueto tumour heterogeneity or assay performance.Conclusions: Cell-free tumour DNA can be detected in plasma and urine, even in patientswith noninvasive disease, with high levels of tumour DNA detectable before progression,especially in urine samples. Personalised assays of genomic variants may be useful fordisease monitoring.Patient summary: Tumour DNA can be detected in blood and urine in early and advancedstages of bladder cancer. Measurement of these highly tumour-specific biomarkers mayrepresent a novel diagnostic tool to indicate the presence of residual disease or to discoveraggressive forms of bladder cancer early in the disease course.

KW - Biomarker; Cell-free DNA; Circulating DNA; Droplet digital PCR; Genomic variant; Next-generation sequencing; NMIBC; Personalised analysis; Plasma; Urine

U2 - 10.1016/j.eururo.2016.01.007

DO - 10.1016/j.eururo.2016.01.007

M3 - Journal article

JO - European Urology

JF - European Urology

SN - 0302-2838

ER -