Perinnöllinen leiomyomatoosi munuaissolusyöpä – geneettisen syyn ja munuaissyöpäalttiuden tutkimus
Perinnöllinen leiomyomatoosi munuaissolusyöpä (HLRCC): Taudin geenin tunnistaminen ja munuaissyöpäalttiuden karakterisointi
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:
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Review of medical records, x-rays, and tissue slides
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Physical examination and family history
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Skin examination
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Gynecological examination for women
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Interviews with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor
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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
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CT or MRI scans (for participants 15 years of age and older only)
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Skin biopsy (surgical removal of a small sample of skin tissue)
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Cheek swab or mouth rinse to collect cells for genetic analysis
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Medical photographs of lesions
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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.
...
Tutkimuksen yleiskatsaus
Tila
Yksityiskohtainen kuvaus
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:
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Individuals that meet one or more of the following criteria:
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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.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: Deborah A Nielsen, R.N.
- Puhelinnumero: (240) 760-6247
- Sähköposti: deborah.nielsen@nih.gov
Tutki yhteystietojen varmuuskopiointi
- Nimi: W. Marston Linehan, M.D.
- Puhelinnumero: (240) 858-3700
- Sähköposti: linehanm@mail.nih.gov
Opiskelupaikat
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Maryland
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Bethesda, Maryland, Yhdysvallat, 20892
- Rekrytointi
- National Institutes of Health Clinical Center
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Ottaa yhteyttä:
- For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
- Puhelinnumero: 888-624-1937
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Näytteenottomenetelmä
Tutkimusväestö
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.
Kuvaus
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INCLUSION CRITERIA:
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Individuals that meet one or more of the following criteria:
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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
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.
EXCLUSION CRITERIA:
None
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Havaintomallit: CASE_ONLY
- Aikanäkymät: PROSPECTIVE
Kohortit ja interventiot
Ryhmä/Kohortti |
|---|
|
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.) |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations.
Aikaikkuna: on-going
|
Molecular genetic differences between normal and tumorigenic fumarate hydratase (fumerase) mutations. |
on-going
|
|
Determine the clinical manifestations of HLRCC
Aikaikkuna: on-going
|
Collection of blood, urine and/or benign and malignant tissue. |
on-going
|
|
Determine if other genes cause HLRCC.
Aikaikkuna: on-going
|
Molecular genetic differences between normal and tumorigenic cells. |
on-going
|
|
Determine genotype/phenotype correlations.
Aikaikkuna: on-going
|
Detection and expression analysis of gene(s). |
on-going
|
|
Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC.
Aikaikkuna: on-going
|
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.
Aikaikkuna: on-going
|
Collection of blood, urine and/or benign and malignant tissue. |
on-going
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Päätutkija: W. Marston Linehan, M.D., National Cancer Institute (NCI)
Julkaisuja ja hyödyllisiä linkkejä
Yleiset julkaisut
- 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.
- Latif 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.
- Zbar 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.
Hyödyllisiä linkkejä
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvioitu)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Urogenitaaliset sairaudet
- Urogenitaaliset kasvaimet
- Neoplasmat sivustoittain
- Neoplasmat
- Miesten urogenitaaliset sairaudet
- Munuaissairaudet
- Urologiset sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet ja raskauden komplikaatiot
- Neoplasmat histologisen tyypin mukaan
- Urologiset kasvaimet
- Neoplasmat, side- ja pehmytkudokset
- Kasvaimet, lihaskudos
- Munuaisten kasvaimet
- Leiomyoma
Muut tutkimustunnusnumerot
- 030066
- 03-C-0066
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
IPD-suunnitelman kuvaus
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.
IPD-jaon aikakehys
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.
IPD-jaon käyttöoikeuskriteerit
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.
IPD-jakamista tukeva tietotyyppi
- STUDY_PROTOCOL
- MAHLA
- ICF
Lääke- ja laitetiedot, tutkimusasiakirjat
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