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

NCT06194669 | Recruiting DMC

• 1 other identifier: SoMuKT
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Renal Cell; Von Hippel-Lindau Disease

Keywords

Somatic mutations; Whole genome sequencing; Normal kidney

Outcome Measures

Primary Outcomes (1)

• 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.

  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 (1)

• 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)

Study Arms (2)

Controls

Healthy volunteers; patients referring to San Raffaele Hospital for renal/urological conditions other than VHL

Other: Blood and urine sample collection

VHL-disease patients

Individuals with genetic diagnosis of Von Hippel Lindau disease

Other: Blood and urine sample collection

Interventions

Blood and urine sample collection OTHER

One whole blood sample per individual (3 ml) will be collected. Up to 5 urine samples per individual will be collected

Controls; VHL-disease patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with genetic diagnosis of VHL-disease, between 25 and 65, both genders

You may qualify if:

• 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);

You may not qualify if:

• patients with bilateral nephrectomy, in dialysis or kidney transplant; use of nephrotoxic drugs

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• Università Vita-Salute San Raffaele: collaborator

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, urine samples, kidney tumor biopsies, kidney cyst biopsies, normal kidney tissue adjacent to tumor biopsies

MeSH Terms

Conditions

Carcinoma, Renal Cell; von Hippel-Lindau Disease

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Irene Franco, PhD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

• Alessandro Larcher, MD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

• Andrea Salonia, MD

  IRCCS Ospedale San Raffaele

  STUDY CHAIR

Central Study Contacts

Irene Franco, PhD

CONTACT

+39 02 2643 2357; franco.irene@hsr.it

Daniela Canibus, BsC

CONTACT

+39 02 2643 5628; canibus.daniela@hsr.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 8, 2024
• Study Start: June 30, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 10, 2024

Record last verified: 2024-01

Locations

IT (1)