Rare and novel GNAS gene mutations in Chinese patients with thyroid cancer

Abstract Background A large number of novel, rare, and uncharacterized mutations in Tumors including thyroid cancer (TC) have been discovered. In this study, we reported two GNAS mutations in Chinese TC patients, and assessed the functional impact. Methods Two hundred and twenty five formalin‐fixed, paraffin‐embedded (FFPE) tissue specimens from Chinese TC patients were tested by NGS. The functional impact of GNAS mutations was assessed using sorting intolerant from tolerant tools (SIFT), polymorphism phenotyping v2 (POLYPHEN‐2) and the mutation assessor. The GNAS protein structure was modeled by Iterative Threading ASSEmbly Refinement (I‐TASSER), and modeling of mutations was performed and visualised by PyMOL. Results Two somatic missense GNAS gene mutations including a rare c.956A>G(p.D319G) and a novel c.1399G>T(p.A467S) were detected in 225 TC tissues (2/225, 0.89%). The novel GNAS mutation c.1399G>T(p.A467S) was predicted to benign and low impact on the protein. SIFT and Mutation Assessor predicted c.956A>G(p.D319G) will be neutral and have low impact, while Polyphen‐2 indicated the mutation may be probably damaging. c.1399G>T(p.A467S) and c.956A>G(p.D319G) molecular modeling data showed two mutations not changed in Gsα, and showed little predicted effect on protein structure. Conclusions A rare somatic GNAS gene mutations c.956A>G(p.D319G) and a novel somatic GNAS mutation c.1399G>T(p.A467S) were found in the present study, which appeared to be associated with low impact on the protein