Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

Murat, C.; Braga, Patrícia Beltrão; Fortes, Maria Angela Henriques Zanella; Bronstein, Marcello D.; Corrêa-Giannella, Maria Lúcia; Giorgi, Ricardo Rodrigues

doi:10.1590/s0100-879x2012007500115

Cited by 36 publications

(28 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another study examined PIK3CA mutations and genomic amplifications in 33 PAs including ACTH-, GH-, PRL-producing, and NFPAs, and found that PIK3CA mutations were evident in 12.1% of tumors including one noninvasive ACTH tumor. Genomic amplification (defined as copy number R4) was found in 21.2% of cases (Murat et al 2012).…”

Section: Analysis Of the Rtk/pi3k/akt/mtor Pathways In Pamentioning

confidence: 99%

The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas

Monsalves¹,

Juraschka²,

Tateno³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

Pituitary adenomas are common intracranial neoplasms. Patients with these tumors exhibit a wide range of clinically challenging problems, stemming either from results of sellar mass effect in pituitary macroadenoma or the diverse effects of aberrant hormone production by adenoma cells. While some patients are cured/controlled by surgical resection and/or medical therapy, a proportion of patients exhibit tumors that are refractory to current modalities. New therapeutic approaches are needed for these patients. Activation of the AKT/phophotidylinositide-3-kinase pathway, including mTOR activation, is common in human neoplasia, and a number of therapeutic approaches are being employed to neutralize activation of this pathway in human cancer. This review examines the role of this pathway in pituitary tumors with respect to tumor biology and its potential role as a therapeutic target.

show abstract

Section: Analysis Of the Rtk/pi3k/akt/mtor Pathways In Pamentioning

confidence: 99%

The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas

Monsalves¹,

Juraschka²,

Tateno³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Regarding somatic pathogenic variants, until recently, only stimulatory guanine nucleotide (GTP)-binding protein alpha (GNAS) pathogenic variants were known to be causally related to somatotropinoma pathogenesis in a sizeable proportion of cases (16,17). Current genomic techniques allowed the identification of other frequently recurrent somatic genetic alterations -phosphatidylinositol 3 kinase alpha subunit (PIK3AC) gene in various types of pituitary adenomas (18,19) and ubiquitin-specific protease 8 (USP8) (20,21) and USP48 gene pathogenic variants in corticotropinomas (22).…”

Section: Introductionmentioning

confidence: 99%

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Vandeva

Daly

Pétrossians

et al. 2019

European Journal of Endocrinology

View full text Add to dashboard Cite

Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors is a matter of interest as it could help to improve diagnosis and treatment. Until recently, however, disruptions in relatively few genes were known to predispose to pituitary tumor formation. In the last decade, several more genes and pathways have been described. Germline pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene were found in familial or sporadic pituitary adenomas, usually with an aggressive clinical course. Cyclin-dependent kinase inhibitor 1B (CDKN1B) pathogenic variants lead to multiple endocrine neoplasia type 4 (MEN4) syndrome, in which pituitary adenomas can occur. Xq26.3 duplications involving the gene GPR101 cause X-linked acrogigantism. The pheochomocytoma and/or paraganglioma with pituitary adenoma association (3PAs) syndrome suggests that pathogenic variants in the genes of the succinate dehydrogenase complex or MYC-associated factor X (MAX) might be involved in pituitary tumorigenesis. New recurrent somatic alterations were also discovered in pituitary adenomas, such as, ubiquitin-specific protease 8 (USP8) and USP48 pathogenic variants in corticotropinomas. The aim of the present review is to provide an overview of the genetic pathophysiology of pituitary adenomas and their clinical relevance.

show abstract

“…Constitutive activation of the PI3K-AKT-mTOR signaling cascade is also a feature of pituitary adenomas, and is secondary to mutations or amplification of PI3KCA (10,11) or to overexpression of PI3K (12). NFPAs also display activation of the PI3K-AKT-mTOR pathway (13).…”

Section: Introductionmentioning

confidence: 99%

Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas

Lee

Wiedemann

Groß

et al. 2015

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated the antitumor efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in the only available model of spontaneous NFPAs (MENX rats).Experimental Design: Organotypic cultures of rat primary NFPAs were incubated with NVP-BEZ235 and assessed for cell viability, proliferation, apoptosis, and PI3K/mTOR inhibition. NVP-BEZ235, or placebo, was administered to MENX rats and tumor response was monitored noninvasively by diffusion weighted-magnetic resonance imaging (DW-MRI). Following treatment, tumor tissues were investigated for cell proliferation, apoptosis, and PI3K/mTOR inhibition. Genes mediating the cytotoxic activity of NVP-BEZ235 were identified by gene-expression profiling. Among them, Defb1, encoding beta-defensin 1, was further studied for its role in pituitary cells and in human pancreatic neuroendocrine tumor (NET) cells.Results: NVP-BEZ235 showed antiproliferative and pro-cell death activities against NFPAs both in vitro and in vivo, and the response to the drug correlated with inhibition of the PI3K pathway. DW-MRI identified early functional changes (decreased cellularity) in the adenomas before their size was affected and emerged as a useful modality to assess therapy response. The cytotoxic effect of PI3K/mTOR blockade in NFPA was mediated by several genes, including Defb1. NVP-BEZ235 treatment induced Defb1 expression in NFPAs in vitro and in vivo, and in pancreatic NET cells. High Defb1 levels sensitized NET cells to PI3K/mTOR inhibition.Conclusions: Our findings provide rationale for clinical investigation of PI3K/mTOR inhibition in NFPAs and identify novel effectors of PI3K-mediated neuroendocrine cell survival.

show abstract

Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

Cited by 36 publications

References 37 publications

The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas

The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas

Contact Info

Product

Resources

About