Assessment of Residual VHL Function in Tumors - Can it Predict the Patients' Individual Course of Disease?

NCT02207686 | Unknown

• 1 other identifier: H-2-2010-012-A
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators aim to analyze tumors from vHL patients who have different courses of disease and different types of VHL gene alterations to characterize which types of genetic alterations the tumors contain and how these alterations affect the tumor cells' behavior on a molecular level. The investigators will then compare these observations to vHL disease outcome in patients and families. It is already known that most vHL tumors develop when both copies of the VHL gene in a cell are inactivated. The first copy is inactivated in all the person's cells from birth ("first hit"), leaving just one functional copy. A tumor can develop from cells where the second copy is also inactivated ("second hit"). So far, only the molecular consequences of the first hit have been investigated. It is our hypothesis that both the first and second hits in combination have consequences for tumor development and clinical outcome. The investigators will include tumors from patients with different disease courses and different types of "first hits" and analyse the tumors' DNA in order to find correlations between the first and second hits and patients' and families' medical histories. The investigators hereby hope to give new insights into how vHL tumors grow and which genetic factors influence tumor development. These results will contribute to the current knowledge of vHL and help us get one step closer to be able to predict an individual's tumor risks and need for surveillance.

Conditions

Von Hippel-Lindaus Disease

Keywords

CNS hemangioblastoma; Renal Cell Carcinoma; VHL germline mutation; VHL somatic mutation; Tumor development

Outcome Measures

Primary Outcomes (1)

• Residual pVHL activity measured by amount of VHL mRNA in tumor cells

  We will correlate amount of VHL mRNA in tumor cells with the type of the patients' first hit (germline mutation) and the tumor's second hits (somatic mutations).

  Two years

Secondary Outcomes (4)

• Presence of VHL protein (pVHL) in tumor cells

  Two years

• Type of second hit (somatic mutation) found in DNA from tumor cells

  One year

• Patient's age at tumor diagnosis

  Two years

• Patient's total tumor burden

  Two years

Other Outcomes (1)

• Type of clinical vHL in the patient's family (e.g. type 1, type 2)

  Two years

Study Arms (1)

von Hippel-Lindau disease

Patients with von Hippel-Lindau disease who have had at least one vHL-related tumor removed

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

vHL patients over 18 years of age who have had at least one vHL-related tumor removed, and for whom a reference DNA sample (from blood or normal tissue) and tumor tissue (paraffin-embedded or fresh frozen) can be obtained.

You may qualify if:

• vHL diagnosed in patient
• Patient over 18 years of age
• Informed consent to participate can be obtained
• Patient has had at least one vHL-related tumor removed
• A reference DNA sample (from blood or normal tissue) and tumor tissue (paraffin-embedded or fresh frozen) can be obtained.

You may not qualify if:

• Patients under the age of 18 years
• Patients who had not previously had a vHL-related tumor removed
• Patients whos previously removed tumor tissue cannot be obtained or is of such a quantity or quality that no exact histological analysis can be done and/or no DNA can be extracted

Sponsors & Collaborators

• Marie Luise Bisgaard, MD: lead

Study Sites (1)

Department of Cellular and Molecular Medicine, University of Copenhagen

Copenhagen, Copenhagen N, DK-2200, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood Tumor tissue (Paraffin embedded and fresh frozen)

MeSH Terms

Conditions

Carcinoma, Renal Cell

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

Study Officials

• Marie Luise Bisgaard, MD

  Department of Cellular and Molecular Medicine, University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: August 1, 2014
• First Posted: August 4, 2014
• Study Start: September 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2017
• Last Updated: November 13, 2015

Record last verified: 2015-11

Locations

DK (1)