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Int J Mol Sci. 2019 May 30;20(11). pii: E2657. doi: 10.3390/ijms20112657.

DNA-Methylation-Based Detection of Urological Cancer in Urine: Overview of Biomarkers and Considerations on Biomarker Design, Source of DNA, and Detection Technologies.

Author information

1
Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark. louisekl@cancer.dk.
2
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, the Norwegian Radium Hospital, NO-0424 Oslo, Norway. Guro.Elisabeth.Lind@rr-research.no.
3
Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark. perg@cancer.dk.
4
Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark. chd@cancer.dk.

Abstract

Changes in DNA methylation have been causally linked with cancer and provide promising biomarkers for detection in biological fluids such as blood, urine, and saliva. The field has been fueled by genome-wide characterization of DNA methylation across cancer types as well as new technologies for sensitive detection of aberrantly methylated DNA molecules. For urological cancers, urine is in many situations the preferred "liquid biopsy" source because it contains exfoliated tumor cells and cell-free tumor DNA and can be obtained easily, noninvasively, and repeatedly. Here, we review recent advances made in the development of DNA-methylation-based biomarkers for detection of bladder, prostate, renal, and upper urinary tract cancers, with an emphasis on the performance characteristics of biomarkers in urine. For most biomarkers evaluated in independent studies, there was great variability in sensitivity and specificity. We discuss issues that impact the outcome of DNA-methylation-based detection of urological cancer and account for the great variability in performance, including genomic location of biomarkers, source of DNA, and technical issues related to the detection of rare aberrantly methylated DNA molecules. Finally, we discuss issues that remain to be addressed to fully exploit the potential of DNA-methylation-based biomarkers in the clinic, including the need for prospective trials and careful selection of control groups.

KEYWORDS:

DNA methylation biomarkers; bisulfite conversion; bladder cancer; noninvasive detection; prostate cancer; renal cancer; upper urinary tract cancer; urological cancer

PMID:
31151158
DOI:
10.3390/ijms20112657
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