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 carcinoma
(HLRCC) as well as familial renal cancer.
- Studies have led to the identification and characterization of the VHL, HPRC, FLCN
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 variation 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 biologic family members with a suspected or an established diagnosis
of an inherited urologic malignancy in which the disease gene is known, including
von Hippel-Lindau (VHL) and hereditary papillary renal carcinoma (HPRC).
- Individuals and biologic 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.
- Individuals and biologic 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
manifestations and phenotype.
