Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions

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.

Study Overview

• Status: Recruiting
• Conditions: Kidney Neoplasms; Bone Cancer; Thyroid Neoplasms; Pheochromocytoma; Paraganglioma; Other Cancer; Inherited Cancer Syndrome; Associated Conditions
• Intervention / Treatment: Genetic: Genetic screening

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.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Patricia L Dahia, MD,PhD; Phone Number: 2105674866; Email: dahia@uthscsa.edu

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • University of Texas Health Science Center
      • Contact: Patricia L Dahia; Phone Number: 210-567-4866; Email: dahia@uthscsa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Patricia L Dahia, MD, PhD, The University of Texas Health Science Center at San Antonio

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2005
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 17, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: mutation; tumor suppressor gene; oncogene; susceptibility gene
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Genetic Diseases, Inborn; Musculoskeletal Diseases; Thyroid Diseases; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Bone Diseases; Neuroendocrine Tumors; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms; Kidney Neoplasms; Disease; Bone Neoplasms; Thyroid Neoplasms; Pheochromocytoma; Paraganglioma; Neoplastic Syndromes, Hereditary
• Other Study ID Numbers: HSC20060069H; 5R01GM114102 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Aggregate data will be available in the form of publications and pertinent data will be deposited in public depositories

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No