Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions

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.

• Genetic screening (Genetic): Germline and/or tumor samples will be screened for mutations

Primary outcomes

• 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 outcomes

• 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

Sex: All, accepts healthy volunteers

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

• 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. PMID 24442145

• Patricia L Dahia, MD, PhD, Principal investigator, The University of Texas Health Science Center at San Antonio

NIH grants: R01GM114102, R01CA264248