Associated Conditions, Bone Cancer, Inherited Cancer Syndrome, Kidney Neoplasms, Other Cancer, Paraganglioma, Pheochromocytoma, Thyroid Neoplasms
Conditions
Keywords
tumor suppressor gene, oncogene, mutation, susceptibility gene
Brief summary
Pheochromocytomas and paragangliomas are neural crest-derived tumors of the nervous system that are often inherited and genetically heterogeneous. Genetic screening is recommended for patients and their relatives, and can guide clinical decisions. However, a mutation is not found in all cases. The aims of this proposal are to: 1) to map gene(s) involved in pheochromocytoma, and 2) identify genotype-phenotype correlations in patients with pheochromocytoma/paraganglioma of various genetic origins.
Detailed description
Pheochromocytoma and paragangliomas are tumors originated from neuroectoderm cells located in the adrenal or extra-adrenal paraganglia, often leading to increased secretion of hormones known as catecholamines. These tumors represent a potentially curable cause of hypertension and are malignant in about 10-15% of the cases. Approximately 40% of patients with pheochromocytomas and/or paraganglioma have an inherited mutation. In addition, some patients and/or their relatives that are mutation carriers can develop other tumors as part of inherited cancer susceptibility syndromes. Therefore, detection of the susceptibility mutation is important for diagnosis and follow up. However, the susceptibility gene mutation cannot be identified in all cases. Studies that aim to identify novel susceptibility genes for pheochromocytoma are required. The fist aim of this study is to identify novel pheochromocytoma susceptibility genes. Characterization of such gene(s) can improve our understanding of the pathogenesis pheochromocytoma and paraganglioma and have an impact in diagnosis, therapeutic planning and genetic screening of relatives. The second aim of this project is to characterize relationships between mutations and clinical features that can provide insights into clinical surveillance and screening of at-risk individuals.
Interventions
GENETICGenetic screening
Germline and/or tumor samples will be screened for mutations
Sponsors
National Institute of General Medical Sciences (NIGMS)
The Paradifference Foundation
National Cancer Institute (NCI)
The University of Texas Health Science Center at San Antonio
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* diagnosis of pheochromocytoma and or paraganglioma * family member with diagnosis of pheochromocytoma and or paraganglioma * diagnosis of a pheochromocytoma- and or paraganglioma-associated condition * family member with diagnosis of a pheochromocytoma- and or paraganglioma-associated condition
Exclusion criteria
* unconfirmed diagnosis of pheochromocytoma and/or paraganglioma or associated condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of germline driver mutation | through study completion- average time approximately 6 months | Genetic screen detects a mutation that is likely responsible for tumor development |
| Identification of somatic driver mutation | through study completion- average time approximately 6 months | Genetic screen detects a mutation that is likely responsible for tumor development |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Identification of additional, potentially pathogenic genetic variants | through study completion- average time approximately 6 months | Genetic screen detects other mutations with potential pathogenic effects |
| Identification of clinical features other than pheochromocytoma and/or paraganglioma that segregate with disease | through study completion- average time approximately 6 months | Clinical data reveals other features that might associate with the main disease phenotype |
Countries
United States
Contacts
Primary ContactPatricia L Dahia, MD,PhD
Outcome results
None listed