Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions

Study Overview
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Brief Summary
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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
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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.

Official Title
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Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions

Conditions
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Pheochromocytoma, Paraganglioma, Inherited Cancer Syndrome, Associated Conditions, Kidney Neoplasms, Bone Cancer, Thyroid Neoplasms, Other Cancer

Intervention / Treatment
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* Genetic: Genetic screening


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: Genetic screening|Germline and/or tumor samples will be screened for mutations|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of germline driver mutation | Genetic screen detects a mutation that is likely responsible for tumor development | through study completion- average time approximately 6 months | 
| Identification of somatic driver mutation | Genetic screen detects a mutation that is likely responsible for tumor development | through study completion- average time approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of additional, potentially pathogenic genetic variants | Genetic screen detects other mutations with potential pathogenic effects | through study completion- average time approximately 6 months | 
| Identification of clinical features other than pheochromocytoma and/or paraganglioma that segregate with disease | Clinical data reveals other features that might associate with the main disease phenotype | through study completion- average time approximately 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tumor suppressor gene, oncogene, mutation, susceptibility gene