Mechanisms of Somatic Mutation and Tumor Initiation in Pre-malignant Kidney Tubule Cells

N/ARecruitingNCT06194669

IRCCS San Raffaele50 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Carcinoma, Renal Cell Von Hippel-Lindau Disease

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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); Exclusion Criteria: * patients with bilateral nephrectomy, in dialysis or kidney transplant; use of nephrotoxic drugs

Outcomes

Primary Outcomes

Rate of somatic mutation accumulation in normal kidney tubule genomes

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.

Time frame: 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)

Secondary Outcomes

Quantification of pre-cancer cells in urines

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.