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Clinical Trials (PDQ®)

Genetic Study of Patients With Inherited Urologic Malignancies

Basic Trial Information
Entry Criteria
Expected Enrollment
Published Results
Related Publications
Trial Contact Information
Related Information
Registry Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
No phase specifiedGenetics, Natural history/EpidemiologyActive2 and overNCINCI-89-C-0086
NCI-92-AR-0106, NCT00019617

Special Category: NIH Clinical Center trial, NCI Web site featured trial


  1. Characterize the natural and clinical histories of patients with inherited urologic malignancies.
  2. 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.
  3. 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.
  4. Identify and describe unknown or uncharacterized inherited urologic malignancies.

Entry Criteria

Disease Characteristics:

  • Patients or family members of patients in one of the following disease categories:
    • Suspected or established diagnosis of urologic malignant disorder for which genetic defect is known and mutation detection can be implemented, including the following:
      • von Hippel-Lindau (VHL) syndrome
      • Hereditary papillary renal carcinoma, Type I
      • Hereditary papillary renal carcinoma, Type II
      • Birt Hogg Dube syndrome
      • Multiple endocrine neoplasia 2 (MEN2)
    • Suspected or established diagnosis of an inherited urologic malignancy for which the genetic defect is unknown, including but not limited to:
      • Clear cell renal carcinoma
      • Hereditary renal oncocytoma
      • Hereditary chromophobe renal cell carcinoma
    • Urologic malignancy of suspected, but not proven, genetic etiology, including families with more than one individual affected by the same or related cancers

  • Patients or their family members must manifest one or more of the following features in a pattern suggestive of a heritable urologic malignancy:
    • At least one histologically confirmed or suspected renal carcinoma and/or cyst
    • Cerebellar, spinal, medullary, or cerebral hemangioblastomas
    • Retinal angioma
    • Pancreatic neuroendocrine carcinoma, microcystadenoma, and/or cysts
    • Pheochromocytoma
    • Papillary cystadenoma of the epididymis or broad ligament
    • Endolymphatic sac tumor
    • Cutaneous fibrofolliculomas or multiple skin-colored papules
    • History of spontaneous pneumothorax
    • Lung cysts
    • Thyroid carcinoma
    • Intestinal polyposis with or without colon cancer
    • Cutaneous or uterine leiomyoma or uterine leiomyosarcoma or sarcoma

  • Patients, their at-risk family members, or spouses of patients with suspected inherited urologic malignancies who demonstrate one or more of the above clinical findings but who live too far from NIH to be evaluated at the Clinical Center are also eligible*

     [Note: *Local diagnostic testing and blood collection may be necessary]

  • Relatives or spouses enrolled primarily for genetic linkage studies are eligible but will not undergo imaging diagnostic testing

Prior/Concurrent Therapy:

Biologic therapy:

  • Not specified


  • Not specified

Endocrine therapy:

  • Not specified


  • Not specified


  • Not specified

Patient Characteristics:


  • 2 and over

Performance status:

  • Not specified


  • Not specified


  • Not specified


  • Not specified

Expected Enrollment


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.


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.

Published Results

Maranchie JK, Afonso A, Albert PS, et al.: Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location. Hum Mutat 23 (1): 40-6, 2004.[PUBMED Abstract]

Toro JR, Nickerson ML, Wei MH, et al.: Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet 73 (1): 95-106, 2003.[PUBMED Abstract]

Nickerson ML, Warren MB, Toro JR, et al.: Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome. Cancer Cell 2 (2): 157-64, 2002.[PUBMED Abstract]

Pavlovich CP, Walther MM, Eyler RA, et al.: Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol 26 (12): 1542-52, 2002.[PUBMED Abstract]

Zbar B, Alvord WG, Glenn G, et al.: Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dubé syndrome. Cancer Epidemiol Biomarkers Prev 11 (4): 393-400, 2002.[PUBMED Abstract]

Phillips JL, Ghadimi BM, Wangsa D, et al.: Molecular cytogenetic characterization of early and late renal cell carcinomas in von Hippel-Lindau disease. Genes Chromosomes Cancer 31 (1): 1-9, 2001.[PUBMED Abstract]

Schmidt LS, Warren MB, Nickerson ML, et al.: Birt-Hogg-Dubé syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet 69 (4): 876-82, 2001.[PUBMED Abstract]

Related Publications

Linehan WM, Walther MM, Zbar B: The genetic basis of cancer of the kidney. J Urol 170 (6 Pt 1): 2163-72, 2003.[PUBMED Abstract]

Zbar B, Klausner R, Linehan WM: Studying cancer families to identify kidney cancer genes. Annu Rev Med 54: 217-33, 2003.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

William Linehan, MD, Protocol chair
Ph: 301-496-6353

Trial Sites

 Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
 Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office
Ph: 888-NCI-1937

Related Information

Featured trial article
PDQ® clinical trial 030148
PDQ® clinical trial 990053

Registry Information
Official Title  Clinical Manifestations and Molecular Bases of Heritable Urologic Malignant Disorders
Trial Start Date 1999-01-15
Registered in NCT00019617
Date Submitted to PDQ 1999-01-27
Information Last Verified 2009-07-12

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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