title: Detecting circulating tumor DNA in renal cancer: An open challenge.
abstract: Detection of circulating tumor DNA (ctDNA) in blood of cancer patients is regarded as an important step towards personalized medicine and treatment monitoring. In the present study, we investigated the clinical applicability of ctDNA as liquid biopsy in renal cancer.
  
  
  
  ctDNA in serum and plasma samples derived from ccRCC and colon cancer patients as well as ctDNA isolated from RCC xenografts with known VHL mutation status was investigated using next generation sequencing (NGS). Additionally, a Taqman mutation specific assay was used for specific VHL mutation detection in blood.
  
  
  
  In our study, we successfully identified KRAS mutation in colon cancer patients. We also confirmed the presence of specific VHL mutations in ctDNA derived from RCC xenografts indicating the capability of renal tumors to release DNA into the blood circulation. However, we could not detect any VHL mutation in plasma or serum samples derived from nine ccRCC patients. To increase the sensitivity, a VHL mutation specific Taqman assay was tested. With this approach, the pVHL mutation p.Val130Leu in exon 2 in one patient was successfully detected.
  
  
  
  These data suggest a reduced tumor DNA shedding and an increased clearance of the tumor DNA from the circulation in renal cancer patients independently of tumor size, metastases, and necrosis. This implies that highly sensitive detection methods for mutation calling and prior knowledge of the mutation are required for liquid biopsies in ccRCC.
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Corrò
authors.affiliation: Institute of Physiology, University of Zurich, Switzerland.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hejhal
authors.affiliation: Department of Urology, University Hospital Zurich, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Poyet
authors.affiliation: Department of Urology, University Hospital Zurich, Switzerland.
authors.forename: Tullio
authors.initials: T
authors.lastname: Sulser
authors.affiliation: Department of Urology, University Hospital Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermanns
authors.affiliation: Department of Oncology, University Hospital Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Winder
authors.affiliation: Department of Oncology, University Hospital Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Prager
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
authors.affiliation: Institute of Physiology, University of Zurich, Switzerland.
authors.forename: Ian
authors.initials: I
authors.lastname: Frew
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Switzerland. Electronic address: Markus.Rechsteiner@usz.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Rechsteiner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000097:blood*; D005091:Exons; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood* / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D016283:Proto-Oncogene Proteins p21(ras); C497446:VHL protein, human
keywords: Circulating tumor DNA; Clear cell RCC; Colon cancer; KRAS; Next generation sequencing; VHL