Authors: Pamela U Freda Wendy K Chung Naoki Matsuoka Jane E Walsh M Nabi Kanibir George Kleinman Yuanjia Wang Jeffrey N Bruce Kalmon D Post
Publish Date: 2007/06/27
Volume: 10, Issue: 3, Pages: 275-282
Abstract
Although the molecular mechanisms underlying GH secreting pituitary tumor formation are not well understood mutations in the αsubunit of the stimulatory G gene GNAS have been identified in up to 40 As these mutations could play a role in tumor growth we screened 60 GH secreting tumors for GNAS mutations and assessed whether mutation status correlated with their clinical and pathological characteristics Tumor specimens obtained at surgery were snap frozen Tumor DNA was extracted and PCR was used to amplify regions containing 2 sites of recurrent activating somatic mutations in codons 201 and 227 in GNAS Amplicons were bidirectionally sequenced and analyzed GNAS mutations were present in 24/60 40 of tumors these were arg201cysn = 15 arg201sern = 2 arg201hisn = 2 gln227leun = 4 gln227argn = 1 Preoperative IGFI levels ageadjusted were higher p = 001 but GH levels were slightly higher p = 018 in mutation positive vs negative groups Mutation positive tumors were somewhat smaller than negative tumors p = 007 The proportion of tumors 2 cm was somewhat less among positive 83 vs negative tumors 25 p = 010 Neither mib proliferation index the proportion of invasive tumors nor surgical remission rates differed in the groups IGFI normalization rate with somatostatin analog therapy was similar in positive 3 of 6 vs negative 3 of 7 patients GH secreting tumors harboring GNAS mutations had higher preoperative IGFI levels somewhat higher preoperative GH levels and tended to be smaller than tumors without mutations Presence of a GNAS mutation did not predict a difference in a proliferation marker surgical remission or response to somatostatin analog therapyFunded by grants from the National Institutes of Health DK02561 DK 073040 and DK064720 to PUF RR00645 to the Columbia University GCRC and the Herbert Irving Clinical Scholars Program to WKC The authors wish to thank Mr Robert Sundeen for expert technical assistance with growth hormone and IGFI measurements Presented in part at the 88th Annual Meeting of The Endocrine Society June 2006
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