|Transcript ID (GRCh37/hg19)||ENST00000371100|
|Genomic Coordinates (GRCh37/hg19)||20:57428921-57428923, 20:57484420-57484422|
|Tumor Type||Primary Site|
This GNAS mutation causes constitutive activation of the G-protein complex and activates adenylate cyclase to produce cyclic-AMP (cAMP) that can activate oncogenic pathways. The R201H mutation in GNAS was thought to both drive tumor progression and confer exceptional chemo-sensitivity in a patient with an unclassified kidney cancer.
Somatic mutations in GNAS are frequently found in intraductal papillary mucinous neoplasms (IPMNs) of pancreas, and have been identified in 41% to 66% of cases. All of these mutations involved codon 201 (R201C or R201H). However, the GNAS mutation was infrequent in typical pancreatic ductal adenocarcinomas (PDAs). These mutations are lead to disruption of the intrinsic hydrolytic activity of Gsα, leading to constitutive activation. GNAS mutations seem to be an early event in IPMN development. The clinical significance of these mutations remains to be established.
GNAS (Guanine Nucleotide Binding Protein, Alpha, Stimulating Activity Polypeptide, G-S-alpha) is a component of the heterotrimeric G protein complex that has been shown to be mutated in less than 1% of myelodysplastic syndrome. Mutations of Arg201 of GNAS are typically activating mutations which have been described in various types of solid tumors and McCune Albright syndrome.
GNAS is a component of the heterotrimeric G-protein complex that has been shown to be mutated in 3-7% of colorectal cancers. Mutations at codon R201 of GNAS are typically activating mutations which have been described in various types of solid tumors. These mutations result in disruption of the intrinsic hydrolytic activity of Gsa, leading to constitutive activation. The clinical significance of these mutations in colorectal cancer remains to be established. Correlation with other clinical and laboratory findings is recommended.