Tumores endócrinos associados às mutações das proteínas Gsalfa e Gi2alfa

Abstract

Many oncogenic mutations promote tumor growth by inducing autonomous activity of proteins that normally transmit proliferative signal initiated by extracellular factors. G proteins are a family of guanine nucleotide binding proteins, which are structurally homologous and widely distributed in eukaryotic cells. They are composed of three different subunits (alpha, beta e gamma). The alpha subunit, which contains the guanine nucleotide-binding site, is unique to each G protein. The G proteins couple an array of seven transmembrane receptors at the cell surface with a variety of intracellular effectors, which produce second messenger molecules. A subset of endocrine tumors, such as GH- or ACTH-secreting pituitary adenomas, functioning thyroid adenomas, adrenocortical and gonadal tumors were associated with somatic activating mutations in the highly conserved codons of the Gs (Arg201 and Gln227) and Gi (Arg179 and Gln205) proteins. These findings indicated that the G proteins play a role as oncogenes, contributing with the human endocrine tumorigenesis.

Genetic analysis of a patient with coexisting acromegaly, thyroid papillary carcinoma and subcutaneous fibroma

“…Various studies have demonstrated the prevalence of gsα mutations in GH-secreting pituitary adenomas varies according to geographical location and genetic background of the population (1–3,7), however, the patient described in the present study demonstrated no mutations in exons 8 and 9 of the gsα gene. Previous studies indicated that the prevalence of gsα mutations in GH-secreting pituitary adenomas varies by the geographical location and the genetic background of the population (7,17).…”

“…Genetic alterations, such as missense mutations in the gene-encoding α-subunit of G protein (gsα) or the MEN1 gene in multiple endocrinologic neoplasia syndrome 1 (MEN1) have been identified in pituitary adenomas (1–5). …”

“…These mutations include the replacement of arginine by cysteine, serine or histidine in codon 201 of exon 8, or the replacement of glutamine by arginine or leucine in codon 227 of exon 9 (1,6,7). Furthermore, a previous study reported that the frequency of gsα mutations in patients with GH-secreting pituitary adenomas ranged between 4.4 and 43% (2,3).…”