Hereditary Leiomyomatosis Renal Cell Cancer - Study of the Genetic Cause and the Predisposition to Renal Cancer
2 other identifiers
observational
1,130
1 country
1
Brief Summary
This study will investigate what causes hereditary leiomyomatosis renal (kidney) cell cancer, or HLRCC, and how the disease is related to the development of kidney tumors. Leiomyomas are benign (non-cancerous) tumors arising from smooth muscle. HLRCC can cause various health problems. Some people develop red bumps on their skin that can be painful at times. Some women with HLRCC can develop leiomyomas of the uterus. In some families, people with HLRCC develop kidney tumors. This study will try to determine:
- What gene changes (mutations) cause HLRCC
- What kind of kidney tumors develop in HLRCC and how they grow
- What the chance is that a person with HLRCC will develop a kidney tumor People with known or suspected HLRCC (and their family members of any age) may be eligible for this study. This includes people in families in which one or more members has skin leiomyoma and kidney cancer; skin leiomyoma and uterine leiomyoma; multiple skin leiomyomas; kidney cancer and uterine leiomyomas, or kidney cancer consistent with HLRCC, including, but not limited to, collecting duct or papillary, type II. Candidates will be screened with a physical examination, family history, and, for affected family members, a review of medical records, including pathology slides and computed tomography (CT) or magnetic resonance imaging (MRI) scans. Participants will undergo tests and procedures that may include the following:
- Review of medical records, x-rays, and tissue slides
- Physical examination and family history
- Skin examination
- Gynecological examination for women
- Interviews with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor
- Blood tests for:
- Genetic research to identify the gene responsible for HLRCC
- Evaluation of liver, kidney, heart, pancreas, and thyroid function
- Complete blood count and clotting profile
- Pregnancy test for pre-menopausal women
- PSA test for prostate cancer in men over age 40
- CT or MRI scans (for participants 15 years of age and older only)
- Skin biopsy (surgical removal of a small sample of skin tissue)
- Cheek swab or mouth rinse to collect cells for genetic analysis
- Medical photographs of lesions
- Questionnaire When the tests are completed, participants will discuss the results with a doctor and possibly a genetic nurse or genetic counselor. The genetic findings will not be revealed to participants because their meaning and implications may not yet be understood. Participants may be asked to return to NIH from every 3 months to every 3 years, depending on their condition, for follow-up examinations and tests.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 17, 2002
CompletedFirst Posted
Study publicly available on registry
December 18, 2002
CompletedStudy Start
First participant enrolled
February 24, 2003
CompletedApril 20, 2026
November 7, 2025
December 17, 2002
April 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations.
Molecular genetic differences between normal and tumorigenic fumarate hydratase (fumerase) mutations.
on-going
Determine the clinical manifestations of HLRCC
Collection of blood, urine and/or benign and malignant tissue.
on-going
Determine if other genes cause HLRCC.
Molecular genetic differences between normal and tumorigenic cells.
on-going
Determine genotype/phenotype correlations.
Detection and expression analysis of gene(s).
on-going
Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC.
Detection and expression analysis of gene(s).
on-going
Define the risk of developing renal cancer, cutaneous leiomyoma and uterine leiomyoma in this hereditary cancer syndrome.
Collection of blood, urine and/or benign and malignant tissue.
on-going
Study Arms (3)
1 / Individuals
Individuals with known or suspected Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)
2 / Family Members
Family members (related by blood) of individuals who have or are suspected of having Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)
3 / Non-Biologic Family Members
Spouses enrolled primarily for linkage analysis (Spouses have been removed from the inclusion criteria for this study. This closed cohort is for spouses previously enrolled on study.)
Eligibility Criteria
An individual (including patient) from a family in which one or more family member have: 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 Papillary, Type II.
You may qualify if:
- Individuals suspected or known to have phenotype or genotype suggestive of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC), such as:
- Cutaneous leiomyoma and kidney cancer; or
- Cutaneous leiomyoma and uterine leiomyoma; or
- Multiple cutaneous leiomyoma; or
- Kidney cancer and uterine leiomyomata; or
- Renal tumor histology consistent with HLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II
- All participants and parents/guardians, for children younger than 18 years of age, must sign an informed consent document indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed.
- Participants must be \>= 2 years of age.
- A relative (related by blood) of an individual with a confirmed or suspected diagnosis of HLRCC.
You may not qualify if:
- None
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (3)
Linehan WM, Lerman MI, Zbar B. Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer. JAMA. 1995 Feb 15;273(7):564-70. No abstract available.
PMID: 7837390BACKGROUNDLatif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317-20. doi: 10.1126/science.8493574.
PMID: 8493574BACKGROUNDZbar B, Tory K, Merino M, Schmidt L, Glenn G, Choyke P, Walther MM, Lerman M, Linehan WM. Hereditary papillary renal cell carcinoma. J Urol. 1994 Mar;151(3):561-6. doi: 10.1016/s0022-5347(17)35015-2.
PMID: 8308957BACKGROUND
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
W. Marston Linehan, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE ONLY
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 17, 2002
First Posted
December 18, 2002
Study Start
February 24, 2003
Last Updated
April 20, 2026
Record last verified: 2025-11-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.
All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.