The curious case of G\u03b1s gain-of-function in neoplasia

Giulio Innamorati,Claudio Bassi,Havish S Kantheti,Maria Teresa Valenti,Thomas M Wilkie,Marco Parenti,Luca Giacomello,Davide Melisi,Luca Dalle Carbonare

doi:10.1186/s12885-018-4133-z

Abstract

BackgroundMutations activating the α subunit of heterotrimeric Gs protein are associated with a number of highly specific pathological molecular phenotypes. One of the best characterized is the McCune Albright syndrome. The disease presents with an increased incidence of neoplasias in specific tissues.Main bodyA similar repertoire of neoplasms can develop whether mutations occur spontaneously in somatic tissues during fetal development or after birth.Glands are the most “permissive” tissues, recently found to include the entire gastrointestinal tract. High frequency of activating Gαs mutations is associated with precise diagnoses (e.g., IPMN, Pyloric gland adenoma, pituitary toxic adenoma). Typically, most neoplastic lesions, from thyroid to pancreas, remain well differentiated but may be a precursor to aggressive cancer.ConclusionsHere we propose the possibility that gain-of-function mutations of Gαs interfere with signals in the microenvironment of permissive tissues and lead to a transversal neoplastic phenotype.

Highlights

ConclusionsWe propose the possibility that gain-of-function mutations of Gαs interfere with signals in the microenvironment of permissive tissues and lead to a transversal neoplastic phenotype
Mutations activating the α subunit of heterotrimeric Gs protein are associated with a number of highly specific pathological molecular phenotypes
Here we propose the possibility that gain-of-function mutations of Gαs interfere with signals in the microenvironment of permissive tissues and lead to a transversal neoplastic phenotype

Summary

Conclusions

Gsp is emerging as an oncogene acting in multifactorial transformation processes in low-grade or benign neoplasia. It is often associated with papillary morphology and high mucin secretion, reminiscent of previously described endocrine tumors. High Gαs activity may interfere with signaling in immature stages but is not sufficient to progress to invasive carcinoma. Gsp could be a marker for differential diagnosis of early neoplasia

Background

Findings