title: 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.
authors.affiliation: Department of Biophysics, Marmara University School of Medicine, Istanbul, Turkey. bekikan@marmara.edu.tr
authors.forename: Beki
authors.initials: B
authors.lastname: Kan
authors.forename: Christopher
authors.initials: C
authors.lastname: Esapa
authors.forename: Tammam
authors.initials: T
authors.lastname: Sipahi
authors.forename: Cevdet
authors.initials: C
authors.lastname: Nacar
authors.forename: Fahir
authors.initials: F
authors.lastname: Ozer
authors.forename: Nur Buyru
authors.initials: NB
authors.lastname: Sayhan
authors.forename: Mehmet Yaşar
authors.initials: MY
authors.lastname: Kaynar
authors.forename: Ali Cetin
authors.initials: AC
authors.lastname: Sarioğlu
authors.forename: Philip Edward
authors.initials: PE
authors.lastname: Harris
mesh_terms: D000328:Adult; D000483:Alleles; D001345:Autoradiography; D004247:DNA / Q000235:genetics; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D009154:Mutation / Q000502:physiology*; D009841:Oligonucleotides / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014421:Turkey
chemical_list: D009841:Oligonucleotides; D004247:DNA; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs