Telomerase reverse transcriptase promoter mutations in tumors originating from the adrenal gland and extra-adrenal paraganglia
Hotspot mutations in the promoter of the telomerase reverse transcriptase (TERT) gene have been recently reported in human cancers and proposed as a novel mechanism of telomerase activation. To exploreTERTpromoter mutations in tumors originating from the adrenal gland and extra-adrenal paraganglia, a set of 253 tumors (38 adrenocortical carcinomas (ACCs), 127 pheochromocytomas (PCCs), 18 extra-adrenal paragangliomas (ea PGLs), 37 head and neck PGLs (HN PGLs), and 33 peripheral neuroblastic tumors) was selected along with 16 human neuroblastoma (NBL) and two ACC cell lines to assessTERTpromoter mutations by the Sanger sequencing method. All mutations detected were confirmed by a SNaPshot assay. Additionally, 36 gastrointestinal stromal tumors (GISTs) were added to explore an association betweenTERTpromoter mutations and SDH deficiency.TERTpromoter mutations were found in seven out of 289 tumors and in three out of 18 human cell lines; fourC228Tmutations in 38 ACCs (10.5%), twoC228Tmutations in 18 ea PGLs (11.1%), oneC250Tmutation in 36 GISTs (2.8%), and threeC228Tmutations in 16 human NBL cell lines (18.75%). No mutation was detected in PCCs, HN PGLs, neuroblastic tumors as well as ACC cell lines.TERTpromoter mutations preferentially occurred in a SDH-deficient setting (P=0.01) being present in three out of 47 (6.4%) SDH-deficient tumors vs zero out of 171 (0%) SDH-intact tumors. We conclude thatTERTpromoter mutations occur in ACCs and ea PGLs. In addition, preliminary evidence indicates a potential association with the acquisition ofTERTpromoter mutations in SDH-deficient tumors.