title: Role of a p53 polymorphism in the development of nonfunctional pituitary adenomas.
abstract: Non-functional pituitary adenomas (NFPAs) are among the commonest intracranial neoplasms. While histologically benign, NFPAs sometimes become large enough to limit therapeutic options and reduce quality of life. Investigations of the molecular etiology of NFPAs have failed to identify prevalent genetic changes and, while a role for p53 has been suggested, TP53 gene alterations have yet to be described in NFPAs. We found that the polymorphism rs1042522:C > G in codon 72 of exon 4 of the TP53 gene, whose C variant produces a proline and is more common in most ethnicities, has a G variant producing an arginine in 79.8% of NFPAs (n = 42; p < 1.411 × 10-18vs. 1000 Genomes database), causing patients to present a decade earlier with symptomatic NFPAs. In cultured NFPA cells, transfection with the rs1042522 G variant versus the C variant reduced expression of cell arrest gene p21 and increased proliferation. These findings suggest that this TP53 polymorphism influences NFPA growth.
authors.affiliation: University of California, San Francisco (UCSF) Department of Neurological Surgery and Brain Tumor Research Center, 1450 Third Street Room HD-465, San Francisco, CA 94158, USA. Electronic address: Garima.Yagnik@ucsf.edu.
authors.forename: Garima
authors.initials: G
authors.lastname: Yagnik
authors.affiliation: University of California, San Francisco (UCSF) Department of Neurological Surgery and Brain Tumor Research Center, 1450 Third Street Room HD-465, San Francisco, CA 94158, USA.
authors.forename: Arman
authors.initials: A
authors.lastname: Jahangiri
authors.affiliation: University of California, San Francisco (UCSF) Department of Neurological Surgery and Brain Tumor Research Center, 1450 Third Street Room HD-465, San Francisco, CA 94158, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Chen
authors.affiliation: University of California, San Francisco (UCSF) Department of Neurological Surgery and Brain Tumor Research Center, 1450 Third Street Room HD-465, San Francisco, CA 94158, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Wagner
authors.affiliation: University of California, San Francisco (UCSF) Department of Neurological Surgery and Brain Tumor Research Center, 1450 Third Street Room HD-465, San Francisco, CA 94158, USA. Electronic address: Manish.Aghi@ucsf.edu.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Aghi
mesh_terms: D000236:Adenoma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics; D016017:Odds Ratio; D010911:Pituitary Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Pituitary adenoma; Polymorphism; p53