Renal Tumor HistologyNCT00050752
Hereditary Leiomyomatosis Renal Cell Cancer - Study of the Genetic Cause and the Predisposition to Renal Cancer
An observational study of Renal Tumor Histology and Cutaneous Leiomyoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and olderHealthy volunteers can take part
- Conditions the study is for
- Renal Tumor Histology, Cutaneous Leiomyoma, Kidney Cancer
- How many people
- 1,350 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Feb 2003to not given
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: 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.
Who may be able to join
- Individuals that meet one or more of the following criteria:
- 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
Show all 12Show fewer
- OR
- --Renal tumor histology consistent with HLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II
- OR
- --Are a relative (related by blood) of an individual with a confirmed or suspected diagnosis of HLRCC.
- Participants must be >= 2 years of age.
- 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.
Who cannot join
- None
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office, 888-624-1937
About this study
Official title: Hereditary Leiomyomatosis Renal Cell Cancer (HLRCC): Identification of the Disease Gene, and Characterization of the Predisposition to Renal Cancer
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
Read more
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.
Read the detailed description
Background:
- Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a rare autosomal dominantly inherited disorder which confers susceptibility to develop cutaneous and uterine leiomyomas and renal cell carcinoma.
- HLRCC is caused by mutations in the Krebs cycle enzyme, fumarate hydratase localized on chromosome 1q42.3-q43.
Objectives:
- Define the risk of developing renal cancer, cutaneous leiomyoma and uterine leiomyoma in this hereditary cancer syndrome
- Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC
- Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations
- Determine genotype/phenotype correlations
- Determine if other genes cause HLRCC
Eligibility:
- Individuals that meet one or more of the following criteria:
- 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
- Cutaneous leiomyoma and uterine leiomyoma
- Multiple cutaneous leiomyoma
- Kidney cancer and uterine leiomyomata or
-Renal tumor histology consistent with HLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II
or
-Are a relative (related by blood) of an individual with a confirmed or suspected diagnosis of HLRCC
Design:
- These rare biological families will be recruited to genetically confirm diagnosis, determine size and location of renal tumors, size at presentation, growth rate and metastatic potential of renal tumors.
- Genetic testing will be offered to gain appreciation of the effect of mutations on the relative activity of various germline and somatic mutations.
- We will determine if there is a relationship between mutation and disease phenotype.
- Conditions
- Renal Tumor Histology, Cutaneous Leiomyoma, Kidney Cancer
- Keywords
- Renal Cancer, Hereditary Leiomyomatosis, Uterine Fibroid, Cutaneous Leiomyoma, Natural History
- Medical subject headings
- Kidney Neoplasms, Leiomyoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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.) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations.
Molecular genetic differences between normal and tumorigenic fumarate hydratase (fumerase) mutations.
Measured: on-going
Determine the clinical manifestations of HLRCC
Collection of blood, urine and/or benign and malignant tissue.
Measured: on-going
Determine if other genes cause HLRCC.
Molecular genetic differences between normal and tumorigenic cells.
Measured: on-going
Determine genotype/phenotype correlations.
Detection and expression analysis of gene(s).
Measured: on-going
Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC.
Detection and expression analysis of gene(s).
Measured: 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.
Measured: on-going
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2002 (estimated)
- Study start24 Feb 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Renal Tumor HistologyStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 1,350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- W. Marston Linehan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00050752
- Sponsor's protocol ID
- 030066
- Other IDs
- 03-C-0066
- Status last verified
- 15 Oct 2026
- First submitted
- 17 Dec 2002
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 7837390Latif 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.
PubMed 8493574Zbar 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.
PubMed 8308957