Abstract
Pituitary adenomas (PAs) are among the most common intracranial neoplasms, but despite their histologically benign nature, these tumors sometimes grow large enough to cause symptoms of mass effect such as vision loss, headaches, or hypopituitarism. When they get this large, surgery will unfortunately not be curative and, other than prolactinomas, medical options are limited, and radiation has variable efficacy in controlling growth. Understanding the genetic perturbations, such as single nucleotide polymorphisms (SNPs), that promote the formation or growth of functional and nonfunctional PAs is important because such genetic insights could improve the diagnosis and subsequent classification of PAs as well as unlock potential therapeutic targets outside contemporary standard of care. While there have been great strides in the research of SNPs as drivers of PA formation and maintenance, a comprehensive discussion of these genetic mutations has not been undertaken. In the present article, and with the goal of providing scientists and clinicians a central review, we sought to summarize the current literature on SNPs and their relationship to PA formation. Across multiple tumor types, such as nonfunctioning PAs, prolactinomas, corticotroph adenomas, somatotroph adenomas, thyrotropic adenomas, and gonadotroph adenomas, SNPs in cell surface receptors implicated in proliferation can be appreciated. Polymorphisms found in tumor suppressors and cell cycle regulators have also been identified, such as p53 SNPs in nonfunctioning PAs or cyclin D1 in prolactinomas. While the translational relevance of SNPs in the formation of PAs is still in the early stages, the use of wide-scale genomic analysis to identify patients at risk for developing PAs could yield therapeutic benefit in the future.
Highlights
Pituitary adenomas (PAs) are benign neoplasms of the pituitary gland that represent the second most common intracranial tumor with an estimated rate of 3.91–3.97 persons per 100,000 [1,2].The incidence of PAs has been steadily increasing, possibly secondary to an aging population coupled with increased use of surveillance imaging in patients with nonspecific neurologic complaints [3,4].General classification schema delineate PAs based on size, immunohistochemistry staining, secretory endocrine status, and primary cell of origin with type of hormone secreted—in cases of functional PAs [5,6]
single nucleotide polymorphisms (SNPs) seemingly important in functional PAs may not have a role in tumorigenesis of nonfunctioning pituitary adenoma (NFPA), as Hu et al reported when they found that polymorphisms of the AIP gene did not seem to confer any developmental advantage in NFPAs [33]
In 17% and 11% of tumors, respectively [63]. While their results suggested that glucocorticoid receptor (GR) gene polymorphisms play little role in clinical presentation, tumor size, or surgical outcome, SNPs in the GR gene may confer a selective advantage to tumorigenesis in ACTH-secreting tumors
Summary
Pituitary adenomas (PAs) are benign neoplasms of the pituitary gland that represent the second most common intracranial tumor with an estimated rate of 3.91–3.97 persons per 100,000 [1,2]. Clinical manifestation of these neoplasms ranges from headache or neurological deficit due to compression of adjacent structures, such as bitemporal hemianopsia in cases of chiasmal involvement, to hormonal disturbances caused by functional PAs [9]. SNP analysis can be beneficial as a predictive indicator for cancer risk in certain populations where that polymorphism is common. This is in contrast to a mutation, which is any change in the germline or somatic cell DNA sequence that deviates from what is considered normal (detectable in less than 1% of a population). Given the established role of SNPs in various tumors, investigation into their relationship to PA formation and maintenance is warranted
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