Presenter
Samantha Stepanik
Document Type
Poster
Publication Date
2026
Abstract
Pheochromocytoma are rare neuroendocrine tumor of chromaffin cells found in the adrenal medulla; tumors are highly heterogeneous, varying in anatomic location, genetic context, symptomatology, biochemical profile, and metastatic potential. Approximately 30% of pheochromocytoma have a hereditary genetic basis; analysis and classification of pathogenic variants is essential for understanding phenotypic presentation for familial risk assessment and appropriate clinical intervention. Curative treatment for malignant pheochromocytoma does not yet exist; pharmacological intervention is beneficial for symptom management. Pheochromocytoma are categorized into distinct clusters according to underlying genetic alteration, each with unique transcriptional and functional profiles. Cluster 2 includes pathogenic genetic variants involved with kinase signaling pathways, including germline mutation TMEM127. Serving as a key regulatory element of the mTORC1 signaling pathway, inhibiting excessive activation associated with uncontrolled cell growth; suppressing tumor development by promoting RET ubiquitination, positioning, and degradation. Pathogenic germline TMEM127 variants, mapped at chromosome 2q11.2, contribute to 2% of hereditary pheochromocytoma. Lack of expression enhances cell growth signaling, increasing tumor risk. Improper RET stabilization is the mechanism by which TMEM127 loss of function mutations cause pheochromocytoma.
Faculty Mentor
Kristen Rosler, Ph.D.
Academic Discipline
College of Arts & Sciences
Repository Citation
Stepanik, Samantha, "The Genetic Role of TMEM127 in Pheochromocytoma" (2026). Student Research Design & Innovation Symposium. 267.
https://scholarsarchive.jwu.edu/innov_symposium/267
