GNAS R201C

Multiple orthogonal approaches demonstrate that Kras G12D and Gnas R201C co-expression results in a gene signature of gastric pyloric metaplasia and glycolytic dependency during IPMN pathogenesis. The observed metabolic reprogramming may provide a potential target for therapeutics and interception of IPMNs.

Secondly, the presence of the rare pathogenic variants R201S, p.R201G and p.Q227E in 26% (5 out of 19) of myxomas with GNAS pathogenic variants shows that methodologies designed to detect only the common "hotspot" of p.R201C and p.R201H will give false negative results. Finally, a comparison between Ion AmpliSeq Cancer Hotspot Panel v2 and direct cycle Sanger sequencing showed that direct cycle Sanger sequencing provides a quick, reliable, and relatively cheap method to detect GNAS pathogenic variants, matching even the most cutting-edge sequencing methods.

These results reveal BDNF as a new player in the pathogenesis of FD and a potential molecular mechanism by which osteoclastogenesis may be nourished within FD bone lesions. They also suggest that BDNF inhibition may be a new approach to reduce abnormal bone remodeling in FD.

Thus, we identify cell lineage-specific roles for PKA signaling in GNASR201C-driven cell proliferation in pre-cancerous lesions and report the development of a human pancreatic ductal organoid model system to investigate mechanisms regulating GNASR201C-induced IPMNs. Implications: The study identifies an opportunity to discover a PKA-independent pathway downstream of oncogene GNAS for managing IPMN lesions and their progression to PDAC.

Transient pregnancy-induced Cushing's syndrome may be associated with somatic GNAS mutations and altered adrenal pathology due to abnormal activation of LHCGR.

When stratified according to study location, a higher prevalence was observed in Japan (26.8%) while Italy has the lowest (0.4%). Overall prevalence of GNAS gene mutations was 4.8% with codons R201C and R201H being the most mutated, and the results conformed with numerous published studies on GNAS mutation.

Herein, we reported a 73-year-old woman diagnosed with T1N3M1 lung adenocarcinoma harboring EGFR L858R mutation, who acquired two GNAS mutations (R201C and R201H) and lost the EGFR L858R mutation after progression on icotinib and osimertinib. Our study revealed that GNAS R201 can confer the osimertinib resistance in EGFR-positive NSCLC, and present the first report of the prevalence of GNAS R201C and R201H mutants in NSCLC which response to trametinib treatment. Our case suggests that trametinib could be a treatment option in NSCLC patients harboring GNAS-activating mutations.

This study pathologically and genetically confirmed that the primary ovarian borderline tumor was derived from the intestinal component of an ovarian teratoma, and that the subsequent pseudomyxoma peritonei progressed from the primary ovarian tumor. Integrative genomic analysis was useful to identify cellular origin of tumors, as well as to precisely interpret the process of disease progression.

Orthotopic PDX models recapitulate clinical, histologic, and molecular features of AA, including the indolent growth of low-grade and aggressive growth of high-grade tumors. Using this system we identify IP paclitaxel as an active agent for high-grade AA.

Hormone excess (including GH and PRL) could be significantly reduced and the visual deficits are greatly improved after the surgery without the decompression of the optic canal. In addition, MAS-associated pituitary adenomas have a moderate expression of Ki-67 and positive expression of Gsα and PKA C-beta, indicating a mildly proliferative nature of these tumors and the possible linking between MAS and adenomas.

We here describe the first case report to our knowledge of a patient with both acromegaly and achalasia. Association of acromegaly and soft muscle tissue hypertrophy may contribute to achalasia's development. If one of these diagnoses is determined, the other also should be considered along with increased risk of oesophageal and colorectal malignancy.

Compound 12 also inhibited human HDAC1, HDAC2 and HDAC6 like vorinostat. This new analog also showed antiproliferative activity against two colon cancer cell lines genetically resembling pseudomyxoma peritonei (PMP), namely HCT116 GNAS R201C/+ and LS174T (IC 0.6 and 1.4 μΜ, respectively) with potency comparable to vorinostat (IC 1.1 and 2.1 μΜ, respectively).

This case emphasized that pancreatic UC-OGC can provide bland morphology, which is morphologically and immunohistochemically undistinguishable from GCT of the bone and soft tissue. Our study also highlights the importance of genetic analyses in properly diagnosing and managing such patients.

The novel PIK3CA p.I459_T462del mutation is not a catalytically activating mutation, and the GNASp.R201C mutation does not activate the MAPK pathway in murine myoblast lineage cells. While LY3023414 and rapamycin biochemically inhibited the PI3K/AKT pathway significantly, single drug agents did not result in cell death. However, combination therapy involving LY3023414 with doxorubicin and rapamycin with vincristine showed synergistic effect.

Mucinous cell proliferation associated with type 1 CPAM has exceptionally good long-term outcomes if confined within the same lobe of CPAM. A second oncogenic mutation in the GNAS gene may be necessary for progression to malignancy and distant spread.

We successfully established GNAS-mutated human induced pluripotent stem cells with increased cAMP production. Considering the differentiation potential of induced pluripotent stem cells, these cells will be useful as a model for elucidating the pathological mechanisms of GNAS-mutated diseases.

Legal entity responsible for the study: The authors. Funding: Has not received any funding.