Clinical trial NCT03160274: Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Official title: Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pheochromocytoma
Paraganglioma
Inherited Cancer Syndrome
Associated Conditions
Kidney Neoplasms
Bone Cancer
Thyroid Neoplasms
Other Cancer
Keywords: tumor suppressor gene
oncogene
mutation
susceptibility gene
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
name: The Paradifference Foundation
name: National Cancer Institute (NCI)
First posted: 2017-05-19
Enrollment: 2000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Individuals must have confirmed personal or family history of pheochromocytoma, paraganglioma or associated conditions. Relatives of patients with pheochromocytoma and/or paraganglioma are also eligible. Consent form will be obtained from all patients. It is expected that a number of participants in the study will be from outside our institution and also outside U.S.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of germline driver mutation
timeFrame: through study completion- average time approximately 6 months
measure: Identification of somatic driver mutation
timeFrame: through study completion- average time approximately 6 months
Secondary outcomes:
measure: Identification of additional, potentially pathogenic genetic variants
timeFrame: through study completion- average time approximately 6 months
measure: Identification of clinical features other than pheochromocytoma and/or paraganglioma that segregate with disease
timeFrame: through study completion- average time approximately 6 months
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Patricia L Dahia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dahia PL. Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity. Nat Rev Cancer. 2014 Feb;14(2):108-19. doi: 10.1038/nrc3648. Epub 2014 Jan 20.