Clinical Manifestations and Molecular Bases of Heritable Urologic Malignant Disorders - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00001238

Purpose

We will investigate the clinical manifestations and molecular genetic defects of heritable urologic malignant disorders. Families with urologic malignancy with known or suspected genetic basis will be enrolled. Affected individuals or individuals suspected of having a germline urologic malignant disorder will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed in situations in which the genetic basis of the disorder has not been elucidated.

Condition
Hemangioblastoma Hereditary Neoplastic Syndrome Hippel Lindau Disease Neoplasm Renal Cell Carcinoma

Study Type:	Observational
Official Title:	Clinical Manifestations and Molecular Bases of Heritable Urologic Malignant Disorders

Resource links provided by NLM:

Genetics Home Reference related topics: von Hippel-Lindau syndrome Help Me Understand Genetics

MedlinePlus related topics: Cancer Von Hippel-Lindau Disease

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	3500
Study Start Date:	April 1989

Detailed Description:

Background:

Disorders under investigation are: Autosomal dominant inherited urologic malignant disorders including: von - Hippel- Lindau (VHL), hereditary papillary renal cancer (HPRC), Birt Hogg Dube (BHD) and hereditary leiomyomatosis and renal cell acarcinoma (HLRCC) as well as familial renal cancer.
Studies have led to the identification and characterization of the VHL, HPRC, BHD and HLRCC genes.
The genetic etiology of the most common type of inherited kidney cancer, familial renal cancer (FRC), remains to be determined.

Objectives:

To characterize the natural and clinical histories of inherited urologic malignant disorders.
To determine the genetic etiology of hereditary urologic malignant disorders in which the gene defect is unknown, by linkage analysis, positional cloning and evaluation of candidate genes.
To correlate specific mutations and their associated protein domains with disease phenotypic expression based on parameters including presenting age, clinical manifestations, histopathology and rate of recurrence.
To identify and describe as yet unknown or uncharacterized inherited urologic malignant disorders.

Eligibility:

Individuals and family members with a suspected or an established diagnosis of von Hippel-Lindau (VHL) syndrome or hereditary papillary renal carcinoma (HPRC), Type I.
Individuals and family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is not yet known, specifically hereditary forms of Type II papillary renal cancer, clear cell renal carcinoma, renal oncocytoma, chromophobe renal carcinoma or Birt Hogg Dube syndrome.
Individuals and family members who have urologic malignant diseases of suspected, but not proven genetic etiology, including families with more than one individual affected by the same or related cancers.

Design:

These rare families will be recruited to genetically confirm diagnosis, determine size and location of renal tumors, size at presentation, growth rate and metastatic potential of renal tumors.
Genetic testing will be offered to gain appreciation of the effect of mutations on the relative activity of various germline and somatic mutations.
We will determine if there is a relationship between mutation and disease phenotype.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA - Subject Category A:

Category A will include patients, and relatives, who may or may not be affected who will be evaluated in the Warren G. Magnuson Clinical Center. Patients in this category will be eligible if they or their family members manifest one or more of the following features in a pattern suggestive of a heritable urologic malignant disorder:

One or more histologically proven or suspected renal carcinomas and/or cysts
Cerebellar, spinal, medullary or cerebral hemangioblastomas
Retinal angioma

Pancreatic neuro-endocrine carcinoma, microcystadenoma and/or cysts

Pheochromocytoma
Papillary cystadenoma of the epididymis or broad ligament
Endolymphatic sac tumor
Known or suspected cutaneous fibrofolliculomas or multiple skin-colored papules
History of spontaneous pneumothorax
Lung cysts
Thyroid carcinoma
Intestinal polyposis + / - colon cancer
Cutaneous or Uterine leiomyoma or uterine leiomyosarcoma, sarcoma

INCLUSION CRITERIA - Subject Category B:

Category B will include patients, their at-risk relatives and spouses of patients with inherited urologic malignancies with the above listed clinical findings who live at a distance and who will not be evaluated at the Clinical Center. In some cases, local diagnostic testing may be necessary for these individuals in addition to collection of a blood sample for molecular analysis.

INCLUSION CRITERIA - Subject Category C:

Category C will include relatives and spouses who enroll in this study primarily for genetic linkage studies. These individuals will contribute a blood sample for DNA analysis only. No imaging diagnostic testing will be performed on individuals from this category.

EXCLUSION CRITERIA:

Persons unable to give informed consent.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001238

Contacts

Contact: NCI Referral Office	1-888-NCI-1937
Contact: W. Marston Linehan, M.D.	(301) 496-6353	linehanm@mail.nih.gov

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Sub-Investigator: National Cancer Institute Referral Office For more information at the NIH Clinical Center contact

Sponsors and Collaborators

National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Linehan WM, Lerman MI, Zbar B. Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer. JAMA. 1995 Feb 15;273(7):564-70. Review. No abstract available.

Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z, Lubensky I, Dean M, Allikmets R, Chidambaram A, Bergerheim UR, Feltis JT, Casadevall C, Zamarron A, Bernues M, Richard S, Lips CJ, Walther MM, Tsui LC, Geil L, Orcutt ML, Stackhouse T, Zbar B, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet. 1997 May;16(1):68-73.

Zbar B, Brauch H, Talmadge C, Linehan M. Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. Nature. 1987 Jun 25-Jul 1;327(6124):721-4.

ClinicalTrials.gov Identifier:	NCT00001238 History of Changes
Obsolete Identifiers:	NCT00019617
Other Study ID Numbers:	890086, 89-C-0086
Study First Received:	November 3, 1999
Last Updated:	December 30, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Linkage Analysis
Renal Cell Carcinoma
Hemangioblastoma
Familial Kidney Cancer

Von Hippel-Lindau Disease
MR
CT
Gadolinium-DTPA

Additional relevant MeSH terms:

Neoplasms
Carcinoma
Carcinoma, Renal Cell
Von Hippel-Lindau Disease
Neoplastic Syndromes, Hereditary
Hemangioblastoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms

Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neurocutaneous Syndromes
Nervous System Diseases
Angiomatosis
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, Inborn
Hemangioma, Capillary
Hemangioma
Neoplasms, Vascular Tissue

ClinicalTrials.gov processed this record on February 12, 2012