Genetic Study of Patients With Inherited Urologic Malignancies - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00019617

Purpose

RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer.

PURPOSE: Genetic trial to study the genes of patients who have an inherited urologic (genitourinary) malignancy (cancer).

Condition	Intervention
Birt Hogg Dube Syndrome Kidney Cancer Multiple Endocrine Neoplasia 1 and 2 (men1, men2) Von Hippel-Lindau Syndrome	Genetic: DNA ploidy analysis Genetic: genetic linkage analysis Genetic: mutation analysis Genetic: polymorphic microsatellite marker analysis Other: medical chart review

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

Resource links provided by NLM:

Genetics Home Reference related topics: Birt-Hogg-Dubé syndrome multiple endocrine neoplasia von Hippel-Lindau syndrome

MedlinePlus related topics: Cancer Kidney Cancer Von Hippel-Lindau Disease

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	3500
Study Start Date:	January 1999

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	2 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

PATIENT CHARACTERISTICS:

Age:

2 and over

Performance status:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

Not specified

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019617

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

William M. Linehan, MD

NCI - Urologic Oncology Branch

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

Maranchie JK, Afonso A, Albert PS, Kalyandrug S, Phillips JL, Zhou S, Peterson J, Ghadimi BM, Hurley K, Riss J, Vasselli JR, Ried T, Zbar B, Choyke P, Walther MM, Klausner RD, Linehan WM. Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location. Hum Mutat. 2004 Jan;23(1):40-6.

Toro JR, Nickerson ML, Wei MH, Warren MB, Glenn GM, Turner ML, Stewart L, Duray P, Tourre O, Sharma N, Choyke P, Stratton P, Merino M, Walther MM, Linehan WM, Schmidt LS, Zbar B. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet. 2003 Jul;73(1):95-106. Epub 2003 May 22.

Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS. 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-Dube syndrome. Cancer Cell. 2002 Aug;2(2):157-64.

Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, Merino MJ. Renal tumors in the Birt-Hogg-Dube syndrome. Am J Surg Pathol. 2002 Dec;26(12):1542-52.

Zbar B, Alvord WG, Glenn G, Turner M, Pavlovich CP, Schmidt L, Walther M, Choyke P, Weirich G, Hewitt SM, Duray P, Gabril F, Greenberg C, Merino MJ, Toro J, Linehan WM. Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dube syndrome. Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):393-400.

Phillips JL, Ghadimi BM, Wangsa D, Padilla-Nash H, Worrell R, Hewitt S, Walther M, Linehan WM, Klausner RD, Ried T. Molecular cytogenetic characterization of early and late renal cell carcinomas in von Hippel-Lindau disease. Genes Chromosomes Cancer. 2001 May;31(1):1-9.

Schmidt LS, Warren MB, Nickerson ML, Weirich G, Matrosova V, Toro JR, Turner ML, Duray P, Merino M, Hewitt S, Pavlovich CP, Glenn G, Greenberg CR, Linehan WM, Zbar B. Birt-Hogg-Dube syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet. 2001 Oct;69(4):876-82. Epub 2001 Aug 30.

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

Zbar B, Klausner R, Linehan WM. Studying cancer families to identify kidney cancer genes. Annu Rev Med. 2003;54:217-33. Epub 2001 Dec 3. Review.

Study ID Numbers:	CDR0000066885, NCI-89-C-0086, NCI-92-AR-0106
Study First Received:	July 11, 2001
Last Updated:	July 8, 2009
ClinicalTrials.gov Identifier:	NCT00019617 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I renal cell cancer
stage II renal cell cancer
stage III renal cell cancer
stage IV renal cell cancer
clear cell renal cell carcinoma
von Hippel-Lindau syndrome

Birt Hogg Dube syndrome
hereditary papillary renal cell carcinoma
multiple endocrine neoplasia 1 and 2 (MEN1, MEN2)
type 2 papillary renal cell carcinoma
type 1 papillary renal cell carcinoma

Study placed in the following topic categories:

Urinary Tract Neoplasm
Angiomatosis
Urogenital Neoplasms
Urologic Neoplasms
Renal Cancer
Urologic Diseases
Von Hippel-Lindau Disease
Kidney Neoplasms
Kidney Diseases
Multiple Endocrine Neoplasia
Endocrine Gland Neoplasms
Neurocutaneous Syndromes
Birt-Hogg-Dube Syndrome
Kidney Cancer

Chromophil Renal Cell Carcinoma
Von Hippel-Lindau Syndrome
Vascular Diseases
Endocrine System Diseases
Carcinoma
Neoplastic Syndromes, Hereditary
Papillary Renal Cell Carcinoma
Genetic Diseases, Inborn
Carcinoma, Renal Cell
Clear Cell Renal Cell Carcinoma
Endocrinopathy
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Angiomatosis
Neoplasms, Multiple Primary
Urogenital Neoplasms
Urologic Neoplasms
Pathologic Processes
Neoplasms by Site
Von Hippel-Lindau Disease
Urologic Diseases
Kidney Neoplasms
Syndrome
Cardiovascular Diseases
Multiple Endocrine Neoplasia
Kidney Diseases
Endocrine Gland Neoplasms

Neurocutaneous Syndromes
Disease
Neoplasms by Histologic Type
Nervous System Diseases
Vascular Diseases
Endocrine System Diseases
Carcinoma
Neoplasms
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Carcinoma, Renal Cell
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 04, 2009