Hereditary paraganglioma (PGL) is characterized by the development of slow-growing and vascularized tumors anywhere from the skull base to the pelvic floor. The tumors derive from paraganglia, part of the nervous system which is distributed throughout the body. Paraganglia normally function in protecting our body against reduced oxygen tension (hypoxia), bleeding, cold and reduced blood sugar levels. The carotid body (CB), a small organ located where the carotid artery branches in the neck, is one of the most common locations for PGL. The CB functions as an oxygen-sensor and stimulates the cardiopulmonary system in acute hypoxia (a lack of oxygen in the blood). The head and neck and abdominal paraganglia represent the major locations for PGL. Mutations in three genes have been linked to the beginning and development of PGL.
Structural and behavioral features of PGL tumors were markedly similar to the CBs developed by people and animals living at high altitudes (heavier and larger carotid bodies and an increased incidence of carotid body tumors than those living at sea level). This similarity led us to hypothesize that a critical component of oxygen-sensing system of the paraganglionic tissues was rendered inactive by genetic mutations in an oxygen-sensing gene, leading to defective oxygen sensing and cellular proliferation. This theory has since been supported by cellular research and studies connecting altitude and PGL rates in genetically predisposed people.
Identification of the paraganglioma genes was a major turning point in understanding paraganglioma. However, there are many unanswered questions regarding the development and inheritance of these tumors:
Answering these questions will be possible only by continuing our work in collaboration with PGL patients and their families, and the answers will lead researchers to potential therapeutic tools.
Our research plan to address these questions builds upon our previous discovery of SDHD as an important gene in PGL. More specifically, we plan to:
Thus, our study requires:
Findings from clinical testing and advanced studies done in the clinical laboratory on patient samples are an additional source of useful new information on paraganglioma. The program's Genetic Screening activities collect such samples.
About the Paraganglioma (PGL) Genetic Screening Program at UPCI
A research study led by Dr. Baysal seeks recruitment of new subjects with hereditary paragangliomas. This study aims in part to address mechanisms that predispose certain individuals to develop paraganglioma tumors. The patients potentially eligible for this study are:
Patients who meet at least one of these two criteria should contact Dr. Baysal to discuss potential participation in this study.