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The Origin of Tumor DNA in Urine of Urogenital Cancer Patients: Local Shedding and Transrenal Excretion.
Hentschel, Anouk E; van den Helder, Rianne; van Trommel, Nienke E; van Splunter, Annina P; van Boerdonk, Robert A A; van Gent, Mignon D J M; Nieuwenhuijzen, Jakko A; Steenbergen, Renske D M.
Afiliação
  • Hentschel AE; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
  • van den Helder R; Amsterdam UMC, Vrije Universiteit Amsterdam, Urology, Cancer Center Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
  • van Trommel NE; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
  • van Splunter AP; Antoni van Leeuwenhoek/Netherlands Cancer Institute, Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
  • van Boerdonk RAA; Antoni van Leeuwenhoek/Netherlands Cancer Institute, Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
  • van Gent MDJM; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
  • Nieuwenhuijzen JA; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
  • Steenbergen RDM; Amsterdam UMC, Location Amsterdam Medical Center, Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Cancers (Basel) ; 13(3)2021 Jan 31.
Article em En | MEDLINE | ID: mdl-33572525
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Holanda