title: Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma.
abstract: Human pituitary adenomas are the most common intracranial neoplasms. Approximately 5% of them are familial adenomas. Patients with familial tumors carry germline mutations in predisposition genes, including AIP, MEN1 and PRKAR1A. These mutations are extremely rare in sporadic pituitary adenomas, which therefore are caused by different mechanisms. Multiple tumor suppressive genes linked to sporadic tumors have been identified. Their inactivation is caused by epigenetic mechanisms, mainly promoter hypermethylation, and can be placed into two groups based on their functional interaction with tumor suppressors RB or p53. The RB group includes CDKN2A, CDKN2B, CDKN2C, RB1, BMP4, CDH1, CDH13, GADD45B and GADD45G; AIP and MEN1 genes also belong to this group. The p53 group includes MEG3, MGMT, PLAGL1, RASSF1, RASSF3 and SOCS1. We propose that the tumor suppression function of these genes is mainly mediated by the RB and p53 pathways. We also discuss possible tumor suppression mechanisms for individual genes.
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States. Electronic address: aklibanski@partners.org.
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000818:Animals; D044127:Epigenesis, Genetic; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53
keywords: Epigenetic; Genetic mutation; RB; Sporadic pituitary adenoma; Tumor suppression; p53
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