Mutation of SDHB is a Cause of Hypoxia-Related High-Altitude Paraganglioma

摘要: Purpose: Paragangliomas of the head and neck are neuroendocrine tumors associated with germ line mutations tricarboxylic acid cycle–related genes SDHB, SDHC, SDHD , SDHAF2 . Hypoxia is important in most solid tumors, was directly implicated tumorigenesis over 40 years ago when it shown that dwelling at high altitudes increases incidence carotid body hyperplasia paragangliomas. Although recent research has now elucidated several pathways hypoxia paragangliomas, nothing currently known genetics or gene-environment interactions high-altitude paraganglioma. We postulated SDH might play a role these tumors. Experimental Design: Patients from Mexican family, originating resident Guadalajara, were tested for subsequently, SDHB followed by immunohistochemical confirmation loss. Results: Two patients, born between 1,560 2,240 m, found to have including remarkably aggressive recurrent tumor. Mutation analysis identified pathogenic missense mutation exon 7 c.689G>A, p.Arg230His, loss protein confirmed immunohistochemistry. Conclusions: This first report gene paraganglioma altitude. A rapidly very rare finding an carrier, suggesting interaction. Neither patient showed evidence sympathetic Clin Cancer Res; 16(16); 4148–54. ©2010 AACR.