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

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

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.

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