Genetic Study of Patients With Inherited Urologic Malignancies

OBJECTIVES:

- Characterize the natural and clinical histories of patients with inherited urologic
malignancies.

- Determine the genetic etiology of inherited urologic malignancies in which the gene
defect is unknown, using linkage analysis, positional cloning, and evaluation of
candidate genes.

- Correlate specific mutations and associated protein domains with disease phenotypic
expression, in terms of presenting age, clinical manifestations, histopathology, and
rate of recurrence, in this patient population.

- Identify and describe unknown or uncharacterized inherited urologic malignancies.

OUTLINE: Patients undergo genetic counseling and possible genetic testing followed by a
detailed personal and family medical history, complete physical examination, and collection
of blood and tissue samples. If clinically indicated, patients may undergo further
diagnostic studies. Testing may be done over 1-4 days.

Blood and tissue samples are examined for specific mutations by single strand conformational
polymorphism and DNA sequencing. If the genetic basis is unknown, linkage studies using
polymorphic microsatellite markers may be conducted.

All patients receive the results of the clinical tests. Patients with urologic malignancies
for which the genetic defect is known receive their genetic test results, with genetic
counseling available.

Patients with active lesions are followed every 3 months to every 3 years, depending on
clinical status.

PROJECTED ACCRUAL: A total of 3,500 patients will be accrued for this study. This study will
include but is not limited to individuals from specific populations.