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The origin of tumor DNA in urine of urogenital cancer patients: Local shedding and transrenal excretion
- Source :
- Cancers, 13(3):535, 1-11. Multidisciplinary Digital Publishing Institute (MDPI), Cancers, Hentschel, A E, van den Helder, R, van Trommel, N E, van Splunter, A P, van Boerdonk, R A A, van Gent, M D J M, Nieuwenhuijzen, J A & Steenbergen, R D M 2021, ' The origin of tumor DNA in urine of urogenital cancer patients : Local shedding and transrenal excretion ', Cancers, vol. 13, no. 3, 535, pp. 1-11 . https://doi.org/10.3390/cancers13030535, Cancers, Vol 13, Iss 535, p 535 (2021), Volume 13, Issue 3
- Publication Year :
- 2021
-
Abstract
- Simple Summary There is a clinical need for non-invasive methods to detect urogenital cancer, for which urine offers a promising liquid biopsy. Tumor DNA in urine originates from shedding of the local tumor, but may also be excreted transrenally as circulating DNA fragments from the bloodstream. To assess the origin of tumor-associated DNA in the urine of urogenital cancer patients, molecular tumor markers were tested in natural voided urine, and in urine samples in which contact with the local tumor was circumvented. The latter concerned nephrostomy urine of bladder cancer patients and catheter urine of cervical cancer patients. We demonstrated that tumor DNA in the urine of urogenital cancer patients results not only from the shedding of the local tumor, but also from transrenal excretion of circulating tumor DNA. This supports the great potential of urine as a diagnostic tool for cancer detection. Abstract In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
Urinary system
medicine.medical_treatment
Urology
urogenital neoplasms
Urine
lcsh:RC254-282
Article
Excretion
molecular diagnostics
03 medical and health sciences
0302 clinical medicine
medicine
Liquid biopsy
Urogenital neoplasm
Cervical cancer
Bladder cancer
liquid biopsy
business.industry
biomarkers
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
urine
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Nephrostomy
methylation
mutation
business
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Database :
- OpenAIRE
- Journal :
- Cancers, 13(3):535, 1-11. Multidisciplinary Digital Publishing Institute (MDPI), Cancers, Hentschel, A E, van den Helder, R, van Trommel, N E, van Splunter, A P, van Boerdonk, R A A, van Gent, M D J M, Nieuwenhuijzen, J A & Steenbergen, R D M 2021, ' The origin of tumor DNA in urine of urogenital cancer patients : Local shedding and transrenal excretion ', Cancers, vol. 13, no. 3, 535, pp. 1-11 . https://doi.org/10.3390/cancers13030535, Cancers, Vol 13, Iss 535, p 535 (2021), Volume 13, Issue 3
- Accession number :
- edsair.doi.dedup.....965929753d9d7e6202a04440fb57b146