Role of a p53 polymorphism in the development of nonfunctional pituitary adenomas

- The C variant of the TP53 polymorphism rs1042522 is more common in most ethnicities.
- The G variant of rs1042522 occurs in most nonfunctional pituitary adenomas (NFPAs).
- The G variant of rs1042522 reduces expression of cell arrest gene p21.
- The G variant of rs1042522 increases adenoma cell proliferation.
- The G variant of rs1042522 increases expression of angiogenesis mediator VEGF.

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 × 10−18 vs. 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.