Mechanisms of Somatic Mutation and Tumor Initiation in Pre-malignant Kidney Tubule Cells
- Conditions
- Carcinoma, Renal CellVon Hippel-Lindau Disease
- Interventions
- Other: Blood and urine sample collection
- Registration Number
- NCT06194669
- Lead Sponsor
- IRCCS San Raffaele
- Brief Summary
The goal of this observational study is to analyze somatic mutations in the genome of normal kidney cells from patients affected by kidney cancer predisposition syndrome Von Hippel Lindau (VHL) and compare the mutation rates observed in these patients and in individuals not affected by the disease. The main questions the study aims to answer are:
* Do kidney cells from VHL patients mutate more than cells from control individuals during adult life?
* What mechanisms favor somatic mutation occurrence in the genome of normal kidney tubule cells?
Participants will donate one blood sample and multiple urine samples. Urines will be used for kidney cell isolation, followed by cell culturing and genetic analyses. Urine samples will be collected once a year for 3-5 years. Sample collection will occur during the yearly screening program that each patient undergoes at the hospital. In case patients undergo surgical treatment of kidney tumors, samples discarded from surgery (tumor and normal kidney adjacent to tumor) will be collected and subjected to genetic analyses.
Researchers will compare the number and types of mutations found in tumors and normal kidney cells from VHL-disease patients with those found in normal kidney cells from control individuals, to see if somatic mutation rates are increased in VHL-disease patients during aging.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
- Genetic diagnosis of VHL-disease; age (data need to be collected from a population distributed between 25 and 65 years); gender (males and females should be equally represented);
- patients with bilateral nephrectomy, in dialysis or kidney transplant; use of nephrotoxic drugs
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Controls Blood and urine sample collection Healthy volunteers; patients referring to San Raffaele Hospital for renal/urological conditions other than VHL VHL-disease patients Blood and urine sample collection Individuals with genetic diagnosis of Von Hippel Lindau disease
- Primary Outcome Measures
Name Time Method Rate of somatic mutation accumulation in normal kidney tubule genomes Normal kidney tubule cells from urines are assessed from control and VHL-disease patients typically over a period of 3 years (min 3 months, max 3 years) The genome of multiple normal kidney cells from each subject will be investigated by whole genome sequencing. The number of somatic mutations per genome will be plotted according to donor's age and a curve describing the accumulation of mutations with age will be obtained for both the control and VHL-disease patient populations. The aim is to assess differences in mutation rates in the kidney of VHL-disease patients vs controls and understand the underlying mechanism.
- Secondary Outcome Measures
Name Time Method Quantification of pre-cancer cells in urines Normal kidney tubule cells from urines are assessed from control and VHL-disease patients typically over a period of 3 years (min 3 months, max 3 years) From each urine sample, researchers can culture up to 20 single cell clones and perform a single-clone, gene-expression analysis. The expression of markers that characterize the mutation-prone, pre-cancer population will be assessed in all clones. The fraction of clones expressing markers of pre-cancer cells will be calculated in control and VHL-disease groups. The aim is to assess any differences in the presence of pre-cancer cells in urines from VHL-disease patients vs controls and assess any correlation of this parameter with kidney cancer occurrence.
Trial Locations
- Locations (1)
IRCCS Ospedale San Raffaele
🇮🇹MIlan, Italy