Von Hippel-Lindaus Disease Clinical Trial
Official title:
Assessment of Residual VHL Function in Tumors - Can it Predict the Patients' Individual Course of Disease?
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.
| Status | Enrolling by invitation |
| Enrollment | 50 |
| Est. completion date | August 2017 |
| Est. primary completion date | August 2016 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 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. Exclusion Criteria: - 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 |
Observational Model: Cohort, Time Perspective: Retrospective
| Country | Name | City | State |
|---|---|---|---|
| Denmark | Department of Cellular and Molecular Medicine, University of Copenhagen | Copenhagen | Copenhagen N |
| Lead Sponsor | Collaborator |
|---|---|
| Marie Luise Bisgaard, MD |
Denmark,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Type of clinical vHL in the patient's family (e.g. type 1, type 2) | For each tumor we will correlate the previous outcome measures to the type of clinical vHL found in the patient's family. | Two years | No |
| Primary | 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 | No |
| Secondary | Presence of VHL protein (pVHL) in tumor cells | We will correlated the presence of pVHL in tumor cells with the nature of the patients' (germline mutation) and the tumor cells' second hits (somatic mutations). | Two years | No |
| Secondary | Type of second hit (somatic mutation) found in DNA from tumor cells | We will correlate the type of germline mutation found in the patient's DNA from blood with the types of second hits (somatic mutations) found in the tumor's DNA. | One year | No |
| Secondary | Patient's age at tumor diagnosis | For each tumor we will correlate the previous outcome measures to the patient's age at tumor diagnosis | Two years | No |
| Secondary | Patient's total tumor burden | For each tumor we will correlate the previous outcome measures to the patient's total tumor burden | Two years | No |