Trial Information

Clinical Manifestations and Molecular Bases of Heritable Urologic Malignant Disorders

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.