Although the molecular mechanisms underlying GH secreting
pituitary tumor formation are not well understood, mutations in the alpha-subunit 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 bi-directionally sequenced and analyzed. GNAS mutations were present in 24/60 (40%) of
tumors; these were arg201cys(n = 15), arg201ser(n = 2), arg201his(n = 2), gln227leu(n = 4), gln227arg(n = 1). Preoperative
IGF-I levels (age-adjusted) were higher (p = 0.01), but GH levels were slightly higher (p = 0.18) in mutation positive vs. negative groups. Mutation positive
tumors were somewhat smaller than negative
tumors (p = 0.07). The proportion of
tumors >2 cm was somewhat less among positive (8.3%) vs. negative
tumors (25%) (p = 0.10). Neither mib proliferation index, the proportion of invasive
tumors nor surgical remission rates differed in the groups.
IGF-I 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
IGF-I 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
therapy.