Genetic Study of Cancer Risk and Gene Identification in Patients and Families With Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome - Full Text View

Purpose

RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer and may help doctors identify patients who are at risk for cancer.

PURPOSE: This clinical trial is studying cancer risk and gene identification in patients and families with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC).

Condition	Intervention
Precancerous/Nonmalignant Condition	Procedure: DNA ploidy analysis Procedure: cytogenetic analysis Procedure: gene expression profiling Procedure: genetic linkage analysis Procedure: medical chart review Procedure: mutation analysis

Genetics Home Reference related topics:

hereditary leiomyomatosis and renal cell cancer

MedlinePlus related topics:

Cancer

U.S. FDA Resources

Study Type:	Observational

Official Title:	Hereditary Leiomyomatosis Renal Cell Cancer (HLRCC): Identification Of The Disease Gene And Characterization of The Predisposition To Renal Cancer

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

Estimated Enrollment:	450
Study Start Date:	December 2002

Detailed Description:

OBJECTIVES:

Determine the types and characteristics (e.g., patterns of growth) of renal cancer in patients and families with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.
Determine the risk of renal cancer in patients and their families with HLRCC.
Determine the incidence of germline fumarate hydratase (fumerase) mutations in this population.
Determine whether other genes are responsible for HLRCC.
Correlate genotype and phenotype in this population.
Determine the clinical manifestations of HLRCC.

OUTLINE: Detailed family and medical histories are obtained from participants. Participants then undergo one or more of the following: physical examination, blood draw, imaging studies, and karyotypic analysis.

Blood or buccal smears are examined by linkage or DNA analysis and other genetic studies.

Participants may receive an explanation of study findings, appropriate counseling about their own status, and recommendations for follow-up/treatment. Participants may receive DNA results from analysis of their fumarate hydratase gene.

Some participants with indeterminate renal lesions are followed every 3-36 months, depending on the characteristics (e.g., size and/or growth) of the lesion.

PROJECTED ACCRUAL: A total of 450 participants will be accrued for this study within 3 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Patients with known or suspected hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome and their family members
- Spouses also eligible
One or more family members must have 1 of the following:
- Cutaneous leiomyoma and kidney cancer
- Cutaneous leiomyoma and uterine leiomyoma
- Multiple cutaneous leiomyoma
- Kidney cancer and uterine leiomyomata
- Renal tumor histology consistent with HLRCC, including but not limited to collecting duct and/or type II papillary carcinoma

PATIENT CHARACTERISTICS:

Age

Any age

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

Not specified

Other

Negative pregnancy test (if undergoing imaging tests)

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Concurrent standard-care radiotherapy allowed

Surgery

Concurrent standard-care surgery allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00055627

Locations


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

Sponsors and Collaborators

NCI - Center for Cancer Research-Medical Oncology

National Cancer Institute (NCI)

Investigators


Study Chair:	William M. Linehan, MD	NCI - Urologic Oncology Branch

More Information

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

Publications of Results:

Wei MH, Toure O, Glenn GM, Pithukpakorn M, Neckers L, Stolle C, Choyke P, Grubb R, Middelton L, Turner ML, Walther MM, Merino MJ, Zbar B, Linehan WM, Toro JR. Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet. 2006 Jan;43(1):18-27. Epub 2005 Jun 3.

Isaacs JS, Jung YJ, Mole DR, Lee S, Torres-Cabala C, Chung YL, Merino M, Trepel J, Zbar B, Toro J, Ratcliffe PJ, Linehan WM, Neckers L. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell. 2005 Aug;8(2):143-53.

Other Publications:

Matyakhina L, Freedman RJ, Bourdeau I, Wei MH, Stergiopoulos SG, Chidakel A, Walther M, Abu-Asab M, Tsokos M, Keil M, Toro J, Linehan WM, Stratakis CA. Hereditary leiomyomatosis associated with bilateral, massive, macronodular adrenocortical disease and atypical cushing syndrome: a clinical and molecular genetic investigation. J Clin Endocrinol Metab. 2005 Jun;90(6):3773-9. Epub 2005 Mar 1.

Linehan WM, Zbar B. Focus on kidney cancer. Cancer Cell. 2004 Sep;6(3):223-8. Review. No abstract available. Erratum in: Cancer Cell. 2004 Oct;6(4):423.

Choyke PL, Glenn GM, Walther MM, Zbar B, Linehan WM. Hereditary renal cancers. Radiology. 2003 Jan;226(1):33-46. Review.

Hwang JJ, Uchio EM, Linehan WM, Walther MM. Hereditary kidney cancer. Urol Clin North Am. 2003 Nov;30(4):831-42. Review.

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.

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.

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:	CDR0000269913, NCI-03-C-0066
First Received:	March 6, 2003
Last Updated:	October 18, 2008
ClinicalTrials.gov Identifier:	NCT00055627
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

hereditary leiomyomatosis and renal cell cancer

Study placed in the following topic categories:

Myofibroma

Precancerous Conditions

Leiomyomatosis

Disease Susceptibility

Urogenital Neoplasms

Renal cancer

Kidney cancer

Urologic Neoplasms

Leiomyoma

Carcinoma

Neoplasms, Connective and Soft Tissue

Urologic Diseases

Kidney Neoplasms

Carcinoma, Renal Cell

Genetic Predisposition to Disease

Kidney Diseases

Adenocarcinoma

Urinary tract neoplasm

Leiomyomatosis and renal cell cancer, hereditary

Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms, Muscle Tissue

Neoplasms

Neoplasms by Site

Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 20, 2008

Sponsors and Collaborators:	NCI - Center for Cancer Research-Medical Oncology National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00055627