G Protein Mutations in Pituitary Tumors: A Study on Turkish Patients

Abstract

Activating mutations of the G proteins, Gsalpha (gsp) and Gi2alpha (gip) have been reported in subsets of pituitary tumors. The objective of the study was to assess the frequency of gsp and gip mutations in pituitary tumors from Turkish patients and to investigate the possibility of mutations of protein kinase A catalytic subunit (PKAC) that activates the downstream effectors of adenylyl cyclase. PCR-amplified genomic DNA was analyzed for the presence of mutations in codons 201 and 227 of Gsalpha, codon 179 and 205 of Gi2alpha and codon 196 of PKAC, by single strand conformation polymorphism analysis, allele-specific oligonucleotide hybridization and DNA sequencing. Twenty-two patients from Turkey, 15 females and 7 males were investigated; 7 somatotroph adenomas, 7 clinically non-functioning tumors, 7 prolactinomas and 1 corticotroph adenoma. G protein mutations were identified in 6 of 22 (27.3%) pituitary tumors. Four tumors (3/7 somatotroph adenomas, 43%, 1/7 clinically non-functioning tumor) demonstrated gsp mutations at codon 201 arginine to cysteine and one recurrent somatotroph adenoma demonstrated a mutation of the Gi2alpha gene at codon 193 lysine to arginine. One tumor exhibited a C to T variation in the intervening sequence between codons 179 and 205 of the Gi2alpha gene. No mutations at codon 227 of Gsalpha, codons 179 and 205 of Gi2alpha and codon 196 of the PKAC gene were identified.

Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience

“…Regarding the somatotropinomas, the prevalence of gsp we found is lower than the expected 40%, considering previous series from several countries in the literature [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The reason for such a low prevalence in our series is unknown.…”

“…The results of these studies are summarized in Table 1. In the majority of the series, approximately 40% of the patients present a mutation [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Only four studies assessed the prevalence of the gsp oncogene in NFPA which is around ten percent [5,6,18,20].…”

Impact of <i>gsp</i> Oncogene on the mRNA Content for Somatostatin and Dopamine Receptors in Human Somatotropinomas

“…Depending on the cohort studied, 4.4–55% of sporadic somatotropinomas have been shown to have an activating mutation of the G protein α-subunit gene (GNAS) , known as the gsp oncogene [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. The gsp oncogene arises due to a heterozygous point mutation in the GNAS gene at codon 201 (exon 8), or less frequently at codon 227 (exon 9) [21].…”

Estudo molecular dos genes GNAS, PTTG, AIP, CDKN1B e MEG3 em adenomas hipofisários esporádicos

“…As mutações no códon 201 também foram descritas na literatura como sendo as mais frequentes (54,63,143). A prevalência de gsp + em ACNF foi de 5%, enquanto que em quatro estudos foi de aproximadamente 10% (49,50,53,62). Com relação aos adenomas ACTH, a presença de gsp + foi identificada numa prevalência de 8% corroborando com o resultado de um estudo que encontrou 6% (47).…”

“…Com relação aos adenomas ACTH, a presença de gsp + foi identificada numa prevalência de 8% corroborando com o resultado de um estudo que encontrou 6% (47). Na maioria dos estudos, a presença de gsp + em adenomas GH tem uma prevalência de aproximadamente 40% (53)(54)(55)(56)(57)(58)(59)(60). No presente estudo a prevalência de gsp + em adenomas GH foi de 27%, resultado similar a outros estudos descritos (63,144) Recentemente um estudo demonstrou pela primeira vez uma correlação genótipo-fenótipo com a síndrome NEM1 no qual a variante p.V109G influencia na manifestação clínica de pacientes adultos NEM1 portadores de mutações truncadas no gene MEN1 (170).…”