Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Pheochromocytoma

Von Hippel-Lindau Disease

Kidney Neoplasms

Leiomyomatosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Syndrome

Neurocutaneous Syndromes

Angiomatosis

Vascular Diseases

Ciliopathies

Congenital Abnormalities

Abnormalities, Multiple

Genetic Diseases, Inborn

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Hereditary Renal Cell Carcinoma

Hereditary Leiomyomatosis and Renal Cell Cancer

Patients, biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is known, including VHL and HPRC

Patients and biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is not yet known

Patients and biologic family members with a urologic malignant disease of suspected, but not proven genetic etiology

Deborah A Nielsen, R.N.

W. Marston Linehan, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

We will investigate the clinical manifestations and molecular genetic defects of heritable urologic malignant disorders. Families with urologic malignancy with known or suspected genetic basis will be enrolled. Affected individuals or individuals suspected of having a germline urologic malignant disorder will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed in situations in which the genetic basis of the disorder has not been elucidated.

Background:

* Disorders under investigation are: Autosomal dominant inherited urologic malignant disorders including: von Hippel-Lindau (VHL), hereditary papillary renal cancer (HPRC), Birt Hogg Dube (BHD) and hereditary leiomyomatosis and renal cell acarcinoma (HLRCC) as well as familial renal cancer.
* Studies have led to the identification and characterization of the VHL, HPRC, FLCN and HLRCC genes.
* The genetic etiology of the most common type of inherited kidney cancer, familial renal cancer (FRC), remains to be determined.

Objectives:

* To characterize the natural and clinical histories of inherited urologic malignant disorders.
* To determine the genetic etiology of hereditary urologic malignant disorders in which the gene variation is unknown, by linkage analysis, positional cloning and evaluation of candidate genes.
* To correlate specific mutations and their associated protein domains with disease phenotypic expression based on parameters including presenting age, clinical manifestations, histopathology and rate of recurrence.
* To identify and describe as yet unknown or uncharacterized inherited urologic malignant disorders.

Eligibility:

* Individuals and biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is known, including von Hippel-Lindau (VHL) and hereditary papillary renal carcinoma (HPRC).
* Individuals and biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is not yet known, specifically hereditary forms of Type II papillary renal cancer, clear cell renal carcinoma, renal oncocytoma, chromophobe renal carcinoma or Birt Hogg Dube.
* Individuals and biologic family members who have urologic malignant diseases of suspected, but not proven genetic etiology, including families with more than one individual affected by the same or related cancers.

Design:

* These rare 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 manifestations and phenotype.

Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders

.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.

Collection of blood, tissue \&amp; urine to address further scientific questions related to this protocol.

National Cancer Institute (NCI)

Neoplastic Cells, Circulating

Neoplasm Metastasis

Neoplastic Processes

None- observational study

Alison L Allan, PhD

Circulating tumor cells (CTCs) have prognostic value in several tumor types, and increasing evidence suggests that molecular characterization of CTCs can serve as a "liquid biopsy" to understand and address treatment resistance. The goal of this proposal is to demonstrate that CTCs can be accurately enumerated and characterized in metastatic clear cell renal cancer (CCRC) and can serve as prognostic/predictive biomarkers to improve treatment. The challenge surrounding CTC analysis in CCRC is that most CTC technologies (including the clinical gold-standard CellSearch®) depend in epithelial markers such as EpCAM that are expressed at low or heterogeneous levels in CCRC. Members of the research team have developed a novel CTC microfluidic technology that can effectively detect CTCs that are completely undetectable by CellSearch® because of very low EpCAM expression, as well as allowing for CTC recovery for downstream molecular characterization. The goal of this proposal is therefore to test the hypotheses that (1) The microfluidics CTC technology will have better sensitivity/specificity relative to the CellSearch in metastatic CCRC; and (2) Enumeration of CTCs in metastatic CCRC patients (n=66) will have prognostic value, while molecular characterization of CTCs for expression of biomarkers (VHL, VEGF, mTOR, HIF1/HIF2, AKT) related to CCRC etiology will be predictive of response/resistance to targeted therapies. Although CCRC is relatively uncommon, the lack of established adjuvant treatments and high cost of targeted therapies in the palliative setting makes the search for new prognostic/predictive biomarkers an important clinical goal.

Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer

Prospective Validation of Circulating Tumor Cells (CTCs) and Circulating Endothelial Cells (CECs) as Prognostic Biomarkers in Clear Cell Renal Cancer

For comparison of the 2 CTC platforms, a Bland-Altman plot will be constructed. This plot is superior to standard correlation statistics in that it assesses agreement rather than association. Initially we will use a Chi-Square test to compare the 2 methods at a cutoff point of ≥5 versus \<5 CTCs/7.5mL, with simple comparison of PFS at this level. As the cut-off point may not be the same for each method, we will also compare the methods using simple 2X2 contingency tables.

Survival analysis will be performed by Kaplan Meier and significance analysis will use the log-rank test. Cox multivariate analysis will be performed to look at the number and molecular characteristics of CTCs as independent prognostic parameters of survival.

Radiological assessment of disease status will be carried out as standard-of-care and subjected to correlative analysis relative to CTC status, PFS and OS.

CTCs will be recovered from the microfluidics device and subjected to molecular characterization for expression of markers related to angiogenesis and hypoxia.

CTCs will be enumerated on both the CellSearch and the novel microfluidic device.

London Health Sciences Centre

Hamilton Health Sciences Corporation

Lawson Health Research Institute

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders	NCT00001238	Kidney Cancer Urologic Malign... Renal Cell Carc... Familial Renal ... Clear Cell Rena...		2 Years -	National Institutes of Health Clinical Center (CC)
Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders	NCT00001238	Kidney Cancer Urologic Malign... Renal Cell Carc... Familial Renal ... Clear Cell Rena...		2 Years -	National Institutes of Health Clinical Center (CC)
Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders	NCT00001238	Kidney Cancer Urologic Malign... Renal Cell Carc... Familial Renal ... Clear Cell Rena...		2 Years -	National Institutes of Health Clinical Center (CC)
Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer	NCT02499458	Clear Cell Rena... Circulating Tum... Circulating End... Prognostic Biom... Predictive Biom...	None- observati...	18 Years -	Lawson Health Research Institute
Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer	NCT02499458	Clear Cell Rena... Circulating Tum... Circulating End... Prognostic Biom... Predictive Biom...	None- observati...	18 Years -	Lawson Health Research Institute

Spots Global Cancer Trial Database for clear cell renal cancer