Clinical Manifestations and Molecular Bases of Heritable Urologic Malignant Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00001238
First received: November 3, 1999
Last updated: April 30, 2015
Last verified: April 2015
  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
Kidney Cancer
Urologic Malignant Disorders

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Characterize the natural and clinical histories of inherited urologic malignant disorders. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • Identify and describe as yet unknown or uncharacterized inherited urologic malignant disorders. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 5000
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

Ages Eligible for Study:   2 Years and older
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: W. Marston Linehan, M.D. (301) 496-6353 wl3e@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: W. Marston Linehan, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
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: April 30, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Urologic Malignant Disorders
Birt Hogg Dube
Von Hippel Lindau
Hereditary Papillary Renal Cancer/Renal Cell Acarcinoma

ClinicalTrials.gov processed this record on August 27, 2015