{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:57:13Z","timestamp":1780376233827,"version":"3.54.1"},"reference-count":117,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pituitary"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Non-mutational epigenetic reprogramming is considered an important enabling characteristic of neoplasia. Corticotroph tumors and other subtypes of pituitary tumors are characterized by distinct epigenetic profiles. The DNA methylation profile is consistent with disease-specific gene expression, which highlights the importance of epigenetic changes in tumor formation and progression. Elucidating the epigenetic changes underlying tumorigenesis plays an important role in understanding the molecular pathogenesis of corticotroph tumors and may ultimately contribute to improving tumor-specific treatment. Here, we provide an overview of the epigenetic landscape of corticotroph tumors. We also review the role of epigenetics in silencing the expression of tumor suppressor genes and promoting oncogenes expression, which could potentially be involved in the pathogenesis of corticotroph tumors. We briefly discuss microRNAs and epigenetic aspects of POMC regulation. Lastly, since the epigenetic changes are reversible, we discuss drugs that target epigenetic modifiers that could potentially be used in the arsenal of Cushing\u2019s disease treatment modalities.<\/jats:p>","DOI":"10.1007\/s11102-025-01522-3","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T12:06:06Z","timestamp":1745237166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epigenetic implications in the pathogenesis of corticotroph tumors"],"prefix":"10.1007","volume":"28","author":[{"given":"Ticiana","family":"Paes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo J.","family":"Hofland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand M.","family":"Iyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-391X","authenticated-orcid":false,"given":"Richard A.","family":"Feelders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"issue":"20","key":"1522_CR1","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1056\/NEJMp1508811","volume":"373","author":"B Vogelstein","year":"2015","unstructured":"Vogelstein B, Kinzler KW (2015) The path to cancer --Three strikes and you\u2019re out. N Engl J Med Nov 373(20):1895\u20131898. https:\/\/doi.org\/10.1056\/NEJMp1508811","journal-title":"N Engl J Med Nov"},{"issue":"6","key":"1522_CR2","doi-asserted-by":"publisher","first-page":"e1007362","DOI":"10.1371\/journal.pgen.1007362","volume":"06","author":"A Nebbioso","year":"2018","unstructured":"Nebbioso A, Tambaro FP, Dell\u2019Aversana C, Altucci L (2018) Cancer epigenetics: moving forward. PLoS Genet 06(6):e1007362. https:\/\/doi.org\/10.1371\/journal.pgen.1007362","journal-title":"PLoS Genet"},{"key":"1522_CR3","doi-asserted-by":"publisher","unstructured":"D\u2019Angelo D, De Martino M, Arra C, Fusco A (2019) Emerging role of USP8, HMGA, and Non-Coding RNAs in pituitary tumorigenesis. Cancers (Basel) Sep 11(9). https:\/\/doi.org\/10.3390\/cancers11091302","DOI":"10.3390\/cancers11091302"},{"issue":"1","key":"1522_CR4","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.ccell.2019.11.002","volume":"37","author":"M Neou","year":"2020","unstructured":"Neou M, Villa C, Armignacco R et al (2020) Pangenomic classification of pituitary neuroendocrine tumors. Cancer Cell Jan 37(1):123\u2013134e5. https:\/\/doi.org\/10.1016\/j.ccell.2019.11.002","journal-title":"Cancer Cell Jan"},{"key":"1522_CR5","doi-asserted-by":"publisher","unstructured":"Sbiera S, Kunz M, Weigand I, Deutschbein T, Dandekar T, Fassnacht M (2019) The New Genetic Landscape of Cushing\u2019s Disease: Deubiquitinases in the Spotlight. Cancers (Basel) Nov 11(11). https:\/\/doi.org\/10.3390\/cancers11111761","DOI":"10.3390\/cancers11111761"},{"issue":"5","key":"1522_CR6","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1097\/PPO.0000000000000281","volume":"23","author":"RJ Werner","year":"2017","unstructured":"Werner RJ, Kelly AD, Issa JJ (2017) Epigenetics and precision oncology. Cancer J 2017 Sep\/Oct 23(5):262\u2013269. https:\/\/doi.org\/10.1097\/PPO.0000000000000281","journal-title":"Cancer J 2017 Sep\/Oct"},{"issue":"5","key":"1522_CR7","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1055\/s-0029-1237423","volume":"27","author":"C Dupont","year":"2009","unstructured":"Dupont C, Armant DR, Brenner CA (2009) Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med Sep 27(5):351\u2013357. https:\/\/doi.org\/10.1055\/s-0029-1237423","journal-title":"Semin Reprod Med Sep"},{"key":"1522_CR8","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.brainresbull.2013.07.003","volume":"98","author":"AM Stankiewicz","year":"2013","unstructured":"Stankiewicz AM, Swiergiel AH, Lisowski P (2013) Epigenetics of stress adaptations in the brain. Brain Res Bull Sep 98:76\u201392. https:\/\/doi.org\/10.1016\/j.brainresbull.2013.07.003","journal-title":"Brain Res Bull Sep"},{"issue":"25","key":"1522_CR9","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.2217\/fon-2017-0363","volume":"13","author":"V Holubekova","year":"2017","unstructured":"Holubekova V, Mendelova A, Jasek K, Mersakova S, Zubor P, Lasabova Z (2017) Epigenetic regulation by DNA methylation and MiRNA molecules in cancer. Future Oncol Oct 13(25):2217\u20132222. https:\/\/doi.org\/10.2217\/fon-2017-0363","journal-title":"Future Oncol Oct"},{"key":"1522_CR10","doi-asserted-by":"publisher","unstructured":"Flavahan WA, Gaskell E, Bernstein BE (2017) Epigenetic plasticity and the hallmarks of cancer. Sci Jul 357(6348). https:\/\/doi.org\/10.1126\/science.aal2380","DOI":"10.1126\/science.aal2380"},{"issue":"6","key":"1522_CR11","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1530\/ERC-12-0251","volume":"19","author":"CV Duong","year":"2012","unstructured":"Duong CV, Emes RD, Wessely F, Yacqub-Usman K, Clayton RN, Farrell WE (2012) Quantitative, genome-wide analysis of the DNA methylome in sporadic pituitary adenomas. Endocr Relat Cancer Dec 19(6):805\u2013816. https:\/\/doi.org\/10.1530\/ERC-12-0251","journal-title":"Endocr Relat Cancer Dec"},{"issue":"1","key":"1522_CR12","doi-asserted-by":"publisher","first-page":"19373","DOI":"10.1038\/s41598-020-76555-8","volume":"10","author":"K Taniguchi-Ponciano","year":"2020","unstructured":"Taniguchi-Ponciano K, Andonegui-Elguera S, Pe\u00f1a-Mart\u00ednez E et al (2020) Transcriptome and methylome analysis reveals three cellular origins of pituitary tumors. Sci Rep 11 09 10(1):19373. https:\/\/doi.org\/10.1038\/s41598-020-76555-8","journal-title":"Sci Rep 11 09"},{"issue":"17","key":"1522_CR13","doi-asserted-by":"publisher","first-page":"4126","DOI":"10.1158\/1078-0432.CCR-17-2206","volume":"09","author":"MP Salomon","year":"2018","unstructured":"Salomon MP, Wang X, Marzese DM et al (2018) The epigenomic landscape of pituitary adenomas reveals specific alterations and differentiates among acromegaly, Cushing\u2019s disease and Endocrine-Inactive subtypes. Clin Cancer Res 09(17):4126\u20134136. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-2206","journal-title":"Clin Cancer Res"},{"issue":"8","key":"1522_CR14","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1093\/neuonc\/noab044","volume":"02","author":"MS Mosella","year":"2021","unstructured":"Mosella MS, Sabedot TS, Silva TC et al (2021) DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features. Neuro Oncol Aug 02(8):1292\u20131303. https:\/\/doi.org\/10.1093\/neuonc\/noab044","journal-title":"Neuro Oncol Aug"},{"issue":"1","key":"1522_CR15","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s00401-020-02149-3","volume":"140","author":"FL Ricklefs","year":"2020","unstructured":"Ricklefs FL, Fita KD, Rotermund R et al (2020) Genome-wide DNA methylation profiles distinguish silent from non-silent ACTH adenomas. Acta Neuropathol Jul 140(1):95\u201397. https:\/\/doi.org\/10.1007\/s00401-020-02149-3","journal-title":"Acta Neuropathol Jul"},{"issue":"4","key":"1522_CR16","doi-asserted-by":"publisher","first-page":"e96178","DOI":"10.1371\/journal.pone.0096178","volume":"9","author":"C Ling","year":"2014","unstructured":"Ling C, Pease M, Shi L et al (2014) A pilot genome-scale profiling of DNA methylation in sporadic pituitary macroadenomas: association with tumor invasion and histopathological subtype. PLoS ONE 9(4):e96178. https:\/\/doi.org\/10.1371\/journal.pone.0096178","journal-title":"PLoS ONE"},{"issue":"6","key":"1522_CR17","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1210\/clinem\/dgac703","volume":"17","author":"RMPD Silva-J\u00fanior","year":"2023","unstructured":"Silva-J\u00fanior RMPD, Bueno AC, Martins CS et al (2023) Integrating methylome and transcriptome signatures expands the molecular classification of the pituitary tumors. J Clin Endocrinol Metab May 17(6):1452\u20131463. https:\/\/doi.org\/10.1210\/clinem\/dgac703","journal-title":"J Clin Endocrinol Metab May"},{"key":"1522_CR18","doi-asserted-by":"publisher","first-page":"4841","DOI":"10.12659\/MSM.910608","volume":"24","author":"HS Ma","year":"2018","unstructured":"Ma HS, Wang EL, Xu WF et al (2018) Overexpression of DNA (Cytosine-5)-Methyltransferase 1 (DNMT1) and DNA (Cytosine-5)-Methyltransferase 3A (DNMT3A) is associated with aggressive behavior and hypermethylation of tumor suppressor genes in human pituitary adenomas. Med Sci Monit Jul 24:4841\u20134850. https:\/\/doi.org\/10.12659\/MSM.910608","journal-title":"Med Sci Monit Jul"},{"issue":"3","key":"1522_CR19","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.bbrc.2012.03.035","volume":"420","author":"X Yang","year":"2012","unstructured":"Yang X, Ewald ER, Huo Y et al (2012) Glucocorticoid-induced loss of DNA methylation in non-neuronal cells and potential involvement of DNMT1 in epigenetic regulation of Fkbp5. Biochem Biophys Res Commun Apr 420(3):570\u2013575. https:\/\/doi.org\/10.1016\/j.bbrc.2012.03.035","journal-title":"Biochem Biophys Res Commun Apr"},{"issue":"4","key":"1522_CR20","doi-asserted-by":"publisher","first-page":"T99","DOI":"10.1530\/JME-15-0289","volume":"56","author":"J Drouin","year":"2016","unstructured":"Drouin J (2016) 60 YEARS OF POMC: transcriptional and epigenetic regulation of POMC gene expression. J Mol Endocrinol 05 56(4):T99\u2013T112. https:\/\/doi.org\/10.1530\/JME-15-0289","journal-title":"J Mol Endocrinol 05"},{"issue":"4","key":"1522_CR21","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1136\/jclinpath-2016-203933","volume":"70","author":"JM Pappachan","year":"2017","unstructured":"Pappachan JM, Hariman C, Edavalath M, Waldron J, Hanna FW (2017) Cushing\u2019s syndrome: a practical approach to diagnosis and differential diagnoses. J Clin Pathol Apr 70(4):350\u2013359. https:\/\/doi.org\/10.1136\/jclinpath-2016-203933","journal-title":"J Clin Pathol Apr"},{"issue":"3","key":"1522_CR22","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/nm.3776","volume":"21","author":"M Riebold","year":"2015","unstructured":"Riebold M, Kozany C, Freiburger L et al (2015) A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease. Nat Med Mar 21(3):276\u2013280. https:\/\/doi.org\/10.1038\/nm.3776","journal-title":"Nat Med Mar"},{"issue":"6","key":"1522_CR23","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1210\/jcem.86.6.7563","volume":"86","author":"M Korbonits","year":"2001","unstructured":"Korbonits M, Bujalska I, Shimojo M et al (2001) Expression of 11 beta-hydroxysteroid dehydrogenase isoenzymes in the human pituitary: induction of the type 2 enzyme in corticotropinomas and other pituitary tumors. J Clin Endocrinol Metab Jun 86(6):2728\u20132733. https:\/\/doi.org\/10.1210\/jcem.86.6.7563","journal-title":"J Clin Endocrinol Metab Jun"},{"issue":"6","key":"1522_CR24","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1530\/EJE-07-0428","volume":"157","author":"T Tateno","year":"2007","unstructured":"Tateno T, Izumiyama H, Doi M et al (2007) Differential gene expression in ACTH -secreting and non-functioning pituitary tumors. Eur J Endocrinol Dec 157(6):717\u2013724. https:\/\/doi.org\/10.1530\/EJE-07-0428","journal-title":"Eur J Endocrinol Dec"},{"issue":"20","key":"1522_CR25","doi-asserted-by":"publisher","first-page":"2871","DOI":"10.1101\/gad.1444606","volume":"20","author":"S Bilodeau","year":"2006","unstructured":"Bilodeau S, Vallette-Kasic S, Gauthier Y et al (2006) Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease. Genes Dev Oct 20(20):2871\u20132886. https:\/\/doi.org\/10.1101\/gad.1444606","journal-title":"Genes Dev Oct"},{"issue":"5","key":"1522_CR26","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1210\/endrev\/bnab046","volume":"26","author":"LK Nieman","year":"2022","unstructured":"Nieman LK (2022) Molecular derangements and the diagnosis of ACTH-Dependent Cushing\u2019s syndrome. Endocr Rev Sep 26(5):852\u2013877. https:\/\/doi.org\/10.1210\/endrev\/bnab046","journal-title":"Endocr Rev Sep"},{"issue":"5","key":"1522_CR27","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1210\/en.2013-1868","volume":"155","author":"Y Wu","year":"2014","unstructured":"Wu Y, Patchev AV, Daniel G, Almeida OF, Spengler D (2014) Early-life stress reduces DNA methylation of the Pomc gene in male mice. Endocrinol May 155(5):1751\u20131762. https:\/\/doi.org\/10.1210\/en.2013-1868","journal-title":"Endocrinol May"},{"issue":"2","key":"1522_CR28","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1210\/mend.15.2.0599","volume":"15","author":"J Newell-Price","year":"2001","unstructured":"Newell-Price J, King P, Clark AJ (2001) The CpG Island promoter of the human Proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. Mol Endocrinol Feb 15(2):338\u2013348. https:\/\/doi.org\/10.1210\/mend.15.2.0599","journal-title":"Mol Endocrinol Feb"},{"issue":"9","key":"1522_CR29","doi-asserted-by":"publisher","first-page":"e3346","DOI":"10.1210\/clinem\/dgab387","volume":"106","author":"T Araki","year":"2021","unstructured":"Araki T, Tone Y, Yamamoto M et al (2021) Two distinctive POMC promoters modify gene expression in Cushing disease. J Clin Endocrinol Metab 08 18 106(9):e3346\u2013e3363. https:\/\/doi.org\/10.1210\/clinem\/dgab387","journal-title":"J Clin Endocrinol Metab 08 18"},{"issue":"4","key":"1522_CR30","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s00702-010-0378-7","volume":"117","author":"MA Muschler","year":"2010","unstructured":"Muschler MA, Hillemacher T, Kraus C, Kornhuber J, Bleich S, Frieling H (2010) DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence. J Neural Transm (Vienna) Apr 117(4):513\u2013519. https:\/\/doi.org\/10.1007\/s00702-010-0378-7","journal-title":"J Neural Transm (Vienna) Apr"},{"issue":"7","key":"1522_CR31","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.euroneuro.2018.05.004","volume":"28","author":"M Muschler","year":"2018","unstructured":"Muschler M, Rhein M, Ritter A et al (2018) Epigenetic alterations of the POMC promoter in tobacco dependence. Eur Neuropsychopharmacol Jul 28(7):875\u2013879. https:\/\/doi.org\/10.1016\/j.euroneuro.2018.05.004","journal-title":"Eur Neuropsychopharmacol Jul"},{"issue":"1","key":"1522_CR32","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1210\/mend.13.1.0225","volume":"13","author":"X Zhang","year":"1999","unstructured":"Zhang X, Horwitz GA, Prezant TR et al (1999) Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol Jan 13(1):156\u2013166. https:\/\/doi.org\/10.1210\/mend.13.1.0225","journal-title":"Mol Endocrinol Jan"},{"issue":"3","key":"1522_CR33","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1677\/ERC-08-0012","volume":"15","author":"F Salehi","year":"2008","unstructured":"Salehi F, Kovacs K, Scheithauer BW, Lloyd RV, Cusimano M (2008) Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update. Endocr Relat Cancer Sep 15(3):721\u2013743. https:\/\/doi.org\/10.1677\/ERC-08-0012","journal-title":"Endocr Relat Cancer Sep"},{"issue":"2","key":"1522_CR34","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1210\/er.2006-0042","volume":"28","author":"G Vlotides","year":"2007","unstructured":"Vlotides G, Eigler T, Melmed S (2007) Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. Endocr Rev Apr 28(2):165\u2013186. https:\/\/doi.org\/10.1210\/er.2006-0042","journal-title":"Endocr Rev Apr"},{"issue":"2","key":"1522_CR35","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1046\/j.1365-2265.2003.01598.x","volume":"58","author":"CJ McCabe","year":"2003","unstructured":"McCabe CJ, Khaira JS, Boelaert K et al (2003) Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour. Clin Endocrinol (Oxf) Feb 58(2):141\u2013150. https:\/\/doi.org\/10.1046\/j.1365-2265.2003.01598.x","journal-title":"Clin Endocrinol (Oxf) Feb"},{"issue":"3","key":"1522_CR36","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1007\/s13277-013-0686-2","volume":"34","author":"W Jia","year":"2013","unstructured":"Jia W, Lu R, Jia G, Ni M, Xu Z (2013) Expression of pituitary tumor transforming gene (PTTG) in human pituitary macroadenomas. Tumour Biol Jun 34(3):1559\u20131567. https:\/\/doi.org\/10.1007\/s13277-013-0686-2","journal-title":"Tumour Biol Jun"},{"issue":"4","key":"1522_CR37","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1111\/j.1365-2265.2006.02630.x","volume":"65","author":"M Filippella","year":"2006","unstructured":"Filippella M, Galland F, Kujas M et al (2006) Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study. Clin Endocrinol (Oxf) Oct 65(4):536\u2013543. https:\/\/doi.org\/10.1111\/j.1365-2265.2006.02630.x","journal-title":"Clin Endocrinol (Oxf) Oct"},{"issue":"2","key":"1522_CR38","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1210\/jcem.84.2.5432","volume":"84","author":"X Zhang","year":"1999","unstructured":"Zhang X, Horwitz GA, Heaney AP et al (1999) Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab Feb 84(2):761\u2013767. https:\/\/doi.org\/10.1210\/jcem.84.2.5432","journal-title":"J Clin Endocrinol Metab Feb"},{"key":"1522_CR39","doi-asserted-by":"publisher","first-page":"e213","DOI":"10.1016\/j.wneu.2018.01.214","volume":"113","author":"X Liu","year":"2018","unstructured":"Liu X, Feng M, Zhang Y et al (2018) Expression of matrix Metalloproteinase-9, pituitary tumor transforming gene, high mobility group A 2, and Ki-67 in adrenocorticotropic Hormone-Secreting pituitary tumors and their association with tumor recurrence. World Neurosurg May 113:e213\u2013e221. https:\/\/doi.org\/10.1016\/j.wneu.2018.01.214","journal-title":"World Neurosurg May"},{"key":"1522_CR40","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3389\/fendo.2017.00055","volume":"8","author":"LJ de Ara\u00fajo","year":"2017","unstructured":"de Ara\u00fajo LJ, Lerario AM, de Castro M et al (2017) Transcriptome analysis showed a differential signature between invasive and Non-invasive corticotrophinomas. Front Endocrinol (Lausanne) 8:55. https:\/\/doi.org\/10.3389\/fendo.2017.00055","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"2","key":"1522_CR41","doi-asserted-by":"publisher","first-page":"E17","DOI":"10.3171\/2014.10.FOCUS14683","volume":"38","author":"J Seltzer","year":"2015","unstructured":"Seltzer J, Ashton CE, Scotton TC, Pangal D, Carmichael JD, Zada G (2015) Gene and protein expression in pituitary corticotroph adenomas: a systematic review of the literature. Neurosurg Focus Feb 38(2):E17. https:\/\/doi.org\/10.3171\/2014.10.FOCUS14683","journal-title":"Neurosurg Focus Feb"},{"issue":"12","key":"1522_CR42","doi-asserted-by":"publisher","first-page":"e82619","DOI":"10.1371\/journal.pone.0082619","volume":"8","author":"M Pease","year":"2013","unstructured":"Pease M, Ling C, Mack WJ, Wang K, Zada G (2013) The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature. PLoS ONE 8(12):e82619. https:\/\/doi.org\/10.1371\/journal.pone.0082619","journal-title":"PLoS ONE"},{"issue":"6","key":"1522_CR43","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/S1673-8527(08)60122-8","volume":"36","author":"T Li","year":"2009","unstructured":"Li T, Huang H, Huang B, Lu J (2009) Histone acetyltransferase p300 regulates the expression of human pituitary tumor transforming gene (hPTTG). J Genet Genomics Jun 36(6):335\u2013342. https:\/\/doi.org\/10.1016\/S1673-8527(08)60122-8","journal-title":"J Genet Genomics Jun"},{"issue":"12","key":"1522_CR44","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1507\/endocrj.EJ15-0369","volume":"62","author":"Y Nakada","year":"2015","unstructured":"Nakada Y, Kageyama K, Sugiyama A et al (2015) Inhibitory effects of trichostatin A on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT-20 cells. Endocr J 62(12):1083\u20131090. https:\/\/doi.org\/10.1507\/endocrj.EJ15-0369","journal-title":"Endocr J"},{"key":"1522_CR45","doi-asserted-by":"publisher","unstructured":"Hern\u00e1ndez A, L\u00f3pez-Lluch G, Navas P, Pintor-Toro JA, HDAC (2009) Hsp90 inhibitors down-regulate PTTG1\/securin but do not induce aneuploidy. Genes Chromosomes Cancer Feb 48(2):194\u2013201. https:\/\/doi.org\/10.1002\/gcc.20630","DOI":"10.1002\/gcc.20630"},{"issue":"6","key":"1522_CR46","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1530\/ERC-18-0028","volume":"06","author":"M Fuertes","year":"2018","unstructured":"Fuertes M, Sapochnik M, Tedesco L et al (2018) Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity. Endocr Relat Cancer 06(6):665\u2013676. https:\/\/doi.org\/10.1530\/ERC-18-0028","journal-title":"Endocr Relat Cancer"},{"key":"1522_CR47","doi-asserted-by":"publisher","first-page":"4329","DOI":"10.2147\/OTT.S141345","volume":"10","author":"Y Asari","year":"2017","unstructured":"Asari Y, Kageyama K, Nakada Y et al (2017) Inhibitory effects of a selective Jak2 inhibitor on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT20 cells. Onco Targets Ther 10:4329\u20134338. https:\/\/doi.org\/10.2147\/OTT.S141345","journal-title":"Onco Targets Ther"},{"issue":"1\u20132","key":"1522_CR48","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.mce.2010.04.006","volume":"326","author":"M Labeur","year":"2010","unstructured":"Labeur M, P\u00e1ez-Pereda M, Haedo M, Arzt E, Stalla GK (2010) Pituitary tumors: cell type-specific roles for BMP-4. Mol Cell Endocrinol Sep 326(1\u20132):85\u201388. https:\/\/doi.org\/10.1016\/j.mce.2010.04.006","journal-title":"Mol Cell Endocrinol Sep"},{"issue":"3","key":"1522_CR49","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1210\/en.2009-1102","volume":"151","author":"N Tsukamoto","year":"2010","unstructured":"Tsukamoto N, Otsuka F, Miyoshi T et al (2010) Effects of bone morphogenetic protein (BMP) on adrenocorticotropin production by pituitary Corticotrope cells: involvement of up-regulation of BMP receptor signaling by somatostatin analogs. Endocrinol Mar 151(3):1129\u20131141. https:\/\/doi.org\/10.1210\/en.2009-1102","journal-title":"Endocrinol Mar"},{"issue":"5","key":"1522_CR50","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1210\/me.2004-0425","volume":"19","author":"M Nudi","year":"2005","unstructured":"Nudi M, Ouimette JF, Drouin J (2005) Bone morphogenic protein (Smad)-mediated repression of Proopiomelanocortin transcription by interference with Pitx\/Tpit activity. Mol Endocrinol May 19(5):1329\u20131342. https:\/\/doi.org\/10.1210\/me.2004-0425","journal-title":"Mol Endocrinol May"},{"issue":"1","key":"1522_CR51","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1210\/en.2005-0958","volume":"147","author":"D Giacomini","year":"2006","unstructured":"Giacomini D, P\u00e1ez-Pereda M, Theodoropoulou M et al (2006) Bone morphogenetic protein-4 inhibits corticotroph tumor cells: involvement in the retinoic acid inhibitory action. Endocrinol Jan 147(1):247\u2013256. https:\/\/doi.org\/10.1210\/en.2005-0958","journal-title":"Endocrinol Jan"},{"issue":"8","key":"1522_CR52","doi-asserted-by":"publisher","first-page":"3603","DOI":"10.1210\/en.2012-1231","volume":"153","author":"K Yacqub-Usman","year":"2012","unstructured":"Yacqub-Usman K, Duong CV, Clayton RN, Farrell WE (2012) Epigenomic Silencing of the BMP-4 gene in pituitary adenomas: a potential target for epidrug-induced re-expression. Endocrinol Aug 153(8):3603\u20133612. https:\/\/doi.org\/10.1210\/en.2012-1231","journal-title":"Endocrinol Aug"},{"key":"1522_CR53","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3389\/fendo.2018.00262","volume":"9","author":"M Fuertes","year":"2018","unstructured":"Fuertes M, Tkatch J, Rosmino J, Nieto L, Guitelman MA, Arzt E (2018) New insights in Cushing disease treatment with focus on a derivative of vitamin A. Front Endocrinol (Lausanne) 9:262. https:\/\/doi.org\/10.3389\/fendo.2018.00262","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"1522_CR54","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1530\/JME-19-0059","volume":"63","author":"L Nieto","year":"2019","unstructured":"Nieto L, Fuertes M, Rosmino J, Senin S, Arzt E (2019) Crosstalk of BMP-4 and RA signaling pathways on Pomc gene regulation in corticotrophs. J Mol Endocrinol 10 63(3):161\u2013174. https:\/\/doi.org\/10.1530\/JME-19-0059","journal-title":"J Mol Endocrinol 10"},{"issue":"4","key":"1522_CR55","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/nrc1319","volume":"4","author":"SL Gerson","year":"2004","unstructured":"Gerson SL (2004) MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer Apr 4(4):296\u2013307. https:\/\/doi.org\/10.1038\/nrc1319","journal-title":"Nat Rev Cancer Apr"},{"issue":"5","key":"1522_CR56","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.trecan.2020.02.010","volume":"6","author":"M Butler","year":"2020","unstructured":"Butler M, Pongor L, Su YT et al (2020) MGMT status as a clinical biomarker in glioblastoma. Trends Cancer May 6(5):380\u2013391. https:\/\/doi.org\/10.1016\/j.trecan.2020.02.010","journal-title":"Trends Cancer May"},{"issue":"2","key":"1522_CR57","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1007\/s11102-012-0406-8","volume":"16","author":"A McCormack","year":"2013","unstructured":"McCormack A, Kaplan W, Gill AJ et al (2013) MGMT expression and pituitary tumours: relationship to tumour biology. Pituit Jun 16(2):208\u2013219. https:\/\/doi.org\/10.1007\/s11102-012-0406-8","journal-title":"Pituit Jun"},{"issue":"8","key":"1522_CR58","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1093\/neuonc\/noq017","volume":"12","author":"M Chahal","year":"2010","unstructured":"Chahal M, Xu Y, Lesniak D et al (2010) MGMT modulates glioblastoma angiogenesis and response to the tyrosine kinase inhibitor Sunitinib. Neuro Oncol Aug 12(8):822\u2013833. https:\/\/doi.org\/10.1093\/neuonc\/noq017","journal-title":"Neuro Oncol Aug"},{"issue":"6","key":"1522_CR59","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s11102-017-0829-3","volume":"20","author":"ASG Micko","year":"2017","unstructured":"Micko ASG, W\u00f6hrer A, H\u00f6ftberger R et al (2017) MGMT and MSH6 Immunoexpression for functioning pituitary macroadenomas. Pituit Dec 20(6):643\u2013653. https:\/\/doi.org\/10.1007\/s11102-017-0829-3","journal-title":"Pituit Dec"},{"issue":"2","key":"1522_CR60","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1227\/NEU.0b013e318230ac63","volume":"70","author":"F Salehi","year":"2012","unstructured":"Salehi F, Scheithauer BW, Kovacs K et al (2012) O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemical expression in pituitary corticotroph adenomas. Neurosurg Feb 70(2):491\u2013496 discussion 496. https:\/\/doi.org\/10.1227\/NEU.0b013e318230ac63","journal-title":"Neurosurg Feb"},{"issue":"4","key":"1522_CR61","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1530\/EJE-09-0414","volume":"161","author":"A Takeshita","year":"2009","unstructured":"Takeshita A, Inoshita N, Taguchi M et al (2009) High incidence of low O(6)-methylguanine DNA methyltransferase expression in invasive macroadenomas of Cushing\u2019s disease. Eur J Endocrinol Oct 161(4):553\u2013559. https:\/\/doi.org\/10.1530\/EJE-09-0414","journal-title":"Eur J Endocrinol Oct"},{"issue":"5","key":"1522_CR62","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1002\/cncr.24053","volume":"115","author":"G Widhalm","year":"2009","unstructured":"Widhalm G, Wolfsberger S, Preusser M et al (2009) O(6)-methylguanine DNA methyltransferase Immunoexpression in nonfunctioning pituitary adenomas: are progressive tumors potential candidates for Temozolomide treatment? Cancer Mar 115(5):1070\u20131080. https:\/\/doi.org\/10.1002\/cncr.24053","journal-title":"Cancer Mar"},{"issue":"4","key":"1522_CR63","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s11102-010-0249-0","volume":"13","author":"Q Lau","year":"2010","unstructured":"Lau Q, Scheithauer B, Kovacs K, Horvath E, Syro LV, Lloyd R (2010) MGMT Immunoexpression in aggressive pituitary adenoma and carcinoma. Pituit Dec 13(4):367\u2013379. https:\/\/doi.org\/10.1007\/s11102-010-0249-0","journal-title":"Pituit Dec"},{"issue":"4","key":"1522_CR64","doi-asserted-by":"publisher","first-page":"357","DOI":"10.5114\/fn.2020.102438","volume":"58","author":"P Witek","year":"2020","unstructured":"Witek P, Maksymowicz M, Szamotulska K et al (2020) MGMT expression in pituitary corticotroph adenomas and its relationship to clinical, pathological, and ultrastructural parameters in patients with Cushing\u2019s disease. Folia Neuropathol 58(4):357\u2013364. https:\/\/doi.org\/10.5114\/fn.2020.102438","journal-title":"Folia Neuropathol"},{"issue":"12","key":"1522_CR65","doi-asserted-by":"publisher","first-page":"19674","DOI":"10.18632\/oncotarget.14936","volume":"8","author":"C Dai","year":"2017","unstructured":"Dai C, Sun B, Liu X et al (2017) O-6-Methylguanine-DNA methyltransferase expression is associated with pituitary adenoma tumor recurrence: a systematic meta-analysis. Oncotarget Mar 8(12):19674\u201319683. https:\/\/doi.org\/10.18632\/oncotarget.14936","journal-title":"Oncotarget Mar"},{"issue":"2","key":"1522_CR66","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1111\/j.1365-2265.2008.03487.x","volume":"71","author":"AI McCormack","year":"2009","unstructured":"McCormack AI, McDonald KL, Gill AJ et al (2009) Low O6-methylguanine-DNA methyltransferase (MGMT) expression and response to Temozolomide in aggressive pituitary tumours. Clin Endocrinol (Oxf) Aug 71(2):226\u2013233. https:\/\/doi.org\/10.1111\/j.1365-2265.2008.03487.x","journal-title":"Clin Endocrinol (Oxf) Aug"},{"key":"1522_CR67","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1186\/s12885-015-1595-0","volume":"15","author":"XB Jiang","year":"2015","unstructured":"Jiang XB, Hu B, He DS et al (2015) Expression profiling of O(6) methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases. BMC Cancer Sep 15:644. https:\/\/doi.org\/10.1186\/s12885-015-1595-0","journal-title":"BMC Cancer Sep"},{"key":"1522_CR68","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s13046-014-0056-y","volume":"33","author":"Y Wang","year":"2014","unstructured":"Wang Y, Li J, Tohti M et al (2014) The expression profile of dopamine D2 receptor, MGMT and VEGF in different histological subtypes of pituitary adenomas: a study of 197 cases and indications for the medical therapy. J Exp Clin Cancer Res Jul 33:56. https:\/\/doi.org\/10.1186\/s13046-014-0056-y","journal-title":"J Exp Clin Cancer Res Jul"},{"key":"1522_CR69","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/1471-2407-11-35","volume":"11","author":"M Brell","year":"2011","unstructured":"Brell M, Ib\u00e1\u00f1ez J, Tortosa A (2011) O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction. BMC Cancer Jan 11:35. https:\/\/doi.org\/10.1186\/1471-2407-11-35","journal-title":"BMC Cancer Jan"},{"issue":"10","key":"1522_CR70","doi-asserted-by":"publisher","first-page":"4592","DOI":"10.1210\/jc.2010-0644","volume":"95","author":"G Raverot","year":"2010","unstructured":"Raverot G, Sturm N, de Fraipont F et al (2010) Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience. J Clin Endocrinol Metab Oct 95(10):4592\u20134599. https:\/\/doi.org\/10.1210\/jc.2010-0644","journal-title":"J Clin Endocrinol Metab Oct"},{"issue":"7","key":"1522_CR71","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.prp.2014.02.010","volume":"210","author":"S Arya","year":"2014","unstructured":"Arya S, Majaid MA, Shwetha SD et al (2014) Implications of MGMT methylation status in pituitary adenoma. Pathol Res Pract Jul 210(7):407\u2013411. https:\/\/doi.org\/10.1016\/j.prp.2014.02.010","journal-title":"Pathol Res Pract Jul"},{"issue":"6","key":"1522_CR72","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1530\/EJE-16-0979","volume":"176","author":"H Lasolle","year":"2017","unstructured":"Lasolle H, Cortet C, Castinetti F et al (2017) Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas. Eur J Endocrinol Jun 176(6):769\u2013777. https:\/\/doi.org\/10.1530\/EJE-16-0979","journal-title":"Eur J Endocrinol Jun"},{"issue":"3","key":"1522_CR73","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s11060-011-0532-6","volume":"104","author":"F Salehi","year":"2011","unstructured":"Salehi F, Scheithauer BW, Kros JM et al (2011) MGMT promoter methylation and Immunoexpression in aggressive pituitary adenomas and carcinomas. J Neurooncol Sep 104(3):647\u2013657. https:\/\/doi.org\/10.1007\/s11060-011-0532-6","journal-title":"J Neurooncol Sep"},{"key":"1522_CR74","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1159\/000079037","volume":"32","author":"M Mu\u015fat","year":"2004","unstructured":"Mu\u015fat M, Vax VV, Borboli N et al (2004) Cell cycle dysregulation in pituitary oncogenesis. Front Horm Res 32:34\u201362. https:\/\/doi.org\/10.1159\/000079037","journal-title":"Front Horm Res"},{"issue":"11","key":"1522_CR75","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1210\/mend.13.11.0374","volume":"13","author":"SJ Frost","year":"1999","unstructured":"Frost SJ, Simpson DJ, Clayton RN, Farrell WE (1999) Transfection of an inducible p16\/CDKN2A construct mediates reversible growth Inhibition and G1 arrest in the AtT20 pituitary tumor cell line. Mol Endocrinol Nov 13(11):1801\u20131810. https:\/\/doi.org\/10.1210\/mend.13.11.0374","journal-title":"Mol Endocrinol Nov"},{"issue":"4","key":"1522_CR76","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1002\/path.833","volume":"193","author":"N Seemann","year":"2001","unstructured":"Seemann N, Kuhn D, Wrocklage C et al (2001) CDKN2A\/p16 inactivation is related to pituitary adenoma type and size. J Pathol Apr 193(4):491\u2013497. https:\/\/doi.org\/10.1002\/path.833","journal-title":"J Pathol Apr"},{"issue":"4","key":"1522_CR77","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/(sici)1098-2744(199708)19:4<221::aid-mc1>3.0.co;2-f","volume":"19","author":"M Woloschak","year":"1997","unstructured":"Woloschak M, Yu A, Post KD (1997) Frequent inactivation of the p16 gene in human pituitary tumors by gene methylation. Mol Carcinog Aug 19(4):221\u2013224. https:\/\/doi.org\/10.1002\/(sici)1098-2744(199708)19:4%3C221::aid-mc1%3E3.0.co;2-f","journal-title":"Mol Carcinog Aug"},{"issue":"4","key":"1522_CR78","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1530\/EJE-10-0245","volume":"163","author":"Y Tani","year":"2010","unstructured":"Tani Y, Inoshita N, Sugiyama T et al (2010) Upregulation of CDKN2A and suppression of Cyclin D1 gene expressions in ACTH-secreting pituitary adenomas. Eur J Endocrinol Oct 163(4):523\u2013529. https:\/\/doi.org\/10.1530\/EJE-10-0245","journal-title":"Eur J Endocrinol Oct"},{"issue":"5","key":"1522_CR79","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1158\/1078-0432.ccr-1127-3","volume":"10","author":"DJ Simpson","year":"2004","unstructured":"Simpson DJ, McNicol AM, Murray DC et al (2004) Molecular pathology shows p16 methylation in nonadenomatous pituitaries from patients with Cushing\u2019s disease. Clin Cancer Res Mar 10(5):1780\u20131788. https:\/\/doi.org\/10.1158\/1078-0432.ccr-1127-3","journal-title":"Clin Cancer Res Mar"},{"issue":"1","key":"1522_CR80","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1530\/eje.1.01937","volume":"153","author":"DG Morris","year":"2005","unstructured":"Morris DG, Musat M, Czirj\u00e1k S et al (2005) Differential gene expression in pituitary adenomas by oligonucleotide array analysis. Eur J Endocrinol Jul 153(1):143\u2013151. https:\/\/doi.org\/10.1530\/eje.1.01937","journal-title":"Eur J Endocrinol Jul"},{"issue":"2","key":"1522_CR81","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1007\/s12022-009-9076-0","volume":"20","author":"MG Hossain","year":"2009","unstructured":"Hossain MG, Iwata T, Mizusawa N et al (2009) Expression of p18(INK4C) is down-regulated in human pituitary adenomas. Endocr Pathol 20(2):114\u2013121. https:\/\/doi.org\/10.1007\/s12022-009-9076-0","journal-title":"Endocr Pathol"},{"issue":"2","key":"1522_CR82","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/gcc.20621","volume":"48","author":"M Kirsch","year":"2009","unstructured":"Kirsch M, M\u00f6rz M, Pinzer T, Schackert HK, Schackert G (2009) Frequent loss of the CDKN2C (p18INK4c) gene product in pituitary adenomas. Genes Chromosomes Cancer Feb 48(2):143\u2013154. https:\/\/doi.org\/10.1002\/gcc.20621","journal-title":"Genes Chromosomes Cancer Feb"},{"issue":"2","key":"1522_CR83","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s11060-006-9316-9","volume":"83","author":"A Yoshino","year":"2007","unstructured":"Yoshino A, Katayama Y, Ogino A et al (2007) Promoter hypermethylation profile of cell cycle regulator genes in pituitary adenomas. J Neurooncol Jun 83(2):153\u2013162. https:\/\/doi.org\/10.1007\/s11060-006-9316-9","journal-title":"J Neurooncol Jun"},{"issue":"5","key":"1522_CR84","first-page":"1211","volume":"60","author":"DJ Simpson","year":"2000","unstructured":"Simpson DJ, Hibberts NA, McNicol AM, Clayton RN, Farrell WE (2000) Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG Island. Cancer Res Mar 60(5):1211\u20131216","journal-title":"Cancer Res Mar"},{"key":"1522_CR85","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.mce.2017.07.011","volume":"469","author":"S Ezzat","year":"2018","unstructured":"Ezzat S, Cheng S, Asa SL (2018) Epigenetics of pituitary tumors: pathogenetic and therapeutic implications. Mol Cell Endocrinol 07 469:70\u201376. https:\/\/doi.org\/10.1016\/j.mce.2017.07.011","journal-title":"Mol Cell Endocrinol 07"},{"issue":"2","key":"1522_CR86","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/s0304-3835(98)00013-5","volume":"126","author":"DR Hinton","year":"1998","unstructured":"Hinton DR, Hahn JA, Weiss MH, Couldwell WT (1998) Loss of Rb expression in an ACTH-secreting pituitary carcinoma. Cancer Lett Apr 126(2):209\u2013214. https:\/\/doi.org\/10.1016\/s0304-3835(98)00013-5","journal-title":"Cancer Lett Apr"},{"issue":"1\u20132","key":"1522_CR87","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.mce.2010.03.017","volume":"326","author":"M Mu\u015fat","year":"2010","unstructured":"Mu\u015fat M, Morris DG, Korbonits M, Grossman AB (2010) Cyclins and their related proteins in pituitary tumourigenesis. Mol Cell Endocrinol Sep 326(1\u20132):25\u201329. https:\/\/doi.org\/10.1016\/j.mce.2010.03.017","journal-title":"Mol Cell Endocrinol Sep"},{"issue":"1","key":"1522_CR88","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1530\/eje.0.143r001","volume":"143","author":"S Jordan","year":"2000","unstructured":"Jordan S, Lidhar K, Korbonits M, Lowe DG, Grossman AB (2000) Cyclin D and Cyclin E expression in normal and adenomatous pituitary. Eur J Endocrinol Jul 143(1):R1\u20136. https:\/\/doi.org\/10.1530\/eje.0.143r001","journal-title":"Eur J Endocrinol Jul"},{"issue":"10","key":"1522_CR89","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1210\/jcem.84.10.6066","volume":"84","author":"K Lidhar","year":"1999","unstructured":"Lidhar K, Korbonits M, Jordan S et al (1999) Low expression of the cell cycle inhibitor p27Kip1 in normal corticotroph cells, corticotroph tumors, and malignant pituitary tumors. J Clin Endocrinol Metab Oct 84(10):3823\u20133830. https:\/\/doi.org\/10.1210\/jcem.84.10.6066","journal-title":"J Clin Endocrinol Metab Oct"},{"issue":"10","key":"1522_CR90","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.tem.2015.08.003","volume":"26","author":"S Sbiera","year":"2015","unstructured":"Sbiera S, Deutschbein T, Weigand I, Reincke M, Fassnacht M, Allolio B (2015) The new molecular landscape of Cushing\u2019s disease. Trends Endocrinol Metab Oct 26(10):573\u2013583. https:\/\/doi.org\/10.1016\/j.tem.2015.08.003","journal-title":"Trends Endocrinol Metab Oct"},{"issue":"6","key":"1522_CR91","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1210\/jcem.87.6.8517","volume":"87","author":"M Korbonits","year":"2002","unstructured":"Korbonits M, Chahal HS, Kaltsas G et al (2002) Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors. J Clin Endocrinol Metab Jun 87(6):2635\u20132643. https:\/\/doi.org\/10.1210\/jcem.87.6.8517","journal-title":"J Clin Endocrinol Metab Jun"},{"issue":"6","key":"1522_CR92","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/s41379-018-0016-8","volume":"06","author":"O Mete","year":"2018","unstructured":"Mete O, Cintosun A, Pressman I, Asa SL (2018) Epidemiology and biomarker profile of pituitary adenohypophysial tumors. Mod Pathol 06(6):900\u2013909. https:\/\/doi.org\/10.1038\/s41379-018-0016-8","journal-title":"Mod Pathol"},{"issue":"8","key":"1522_CR93","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1158\/1078-0432.CCR-08-2473","volume":"15","author":"K Horiguchi","year":"2009","unstructured":"Horiguchi K, Yamada M, Satoh T et al (2009) Transcriptional activation of the mixed lineage leukemia-p27Kip1 pathway by a somatostatin analogue. Clin Cancer Res Apr 15(8):2620\u20132629. https:\/\/doi.org\/10.1158\/1078-0432.CCR-08-2473","journal-title":"Clin Cancer Res Apr"},{"issue":"2","key":"1522_CR94","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1677\/JME-08-0146","volume":"42","author":"V Quereda","year":"2009","unstructured":"Quereda V, Malumbres M (2009) Cell cycle control of pituitary development and disease. J Mol Endocrinol Feb 42(2):75\u201386. https:\/\/doi.org\/10.1677\/JME-08-0146","journal-title":"J Mol Endocrinol Feb"},{"key":"1522_CR95","doi-asserted-by":"publisher","unstructured":"Ali Syeda Z, Langden SSS, Munkhzul C, Lee M, Song SJ (2020) Regulatory mechanism of MicroRNA expression in cancer. Int J Mol Sci Mar 21(5). https:\/\/doi.org\/10.3390\/ijms21051723","DOI":"10.3390\/ijms21051723"},{"key":"1522_CR96","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1146\/annurev.neuro.29.051605.112839","volume":"29","author":"X Cao","year":"2006","unstructured":"Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH (2006) Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 29:77\u2013103. https:\/\/doi.org\/10.1146\/annurev.neuro.29.051605.112839","journal-title":"Annu Rev Neurosci"},{"issue":"1","key":"1522_CR97","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/j.1440-1681.2009.05269.x","volume":"37","author":"LM Tsai","year":"2010","unstructured":"Tsai LM, Yu D (2010) MicroRNAs in common diseases and potential therapeutic applications. Clin Exp Pharmacol Physiol Jan 37(1):102\u2013107. https:\/\/doi.org\/10.1111\/j.1440-1681.2009.05269.x","journal-title":"Clin Exp Pharmacol Physiol Jan"},{"issue":"1","key":"1522_CR98","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1210\/jc.2008-1451","volume":"94","author":"FC Amaral","year":"2009","unstructured":"Amaral FC, Torres N, Saggioro F et al (2009) MicroRNAs differentially expressed in ACTH-secreting pituitary tumors. J Clin Endocrinol Metab Jan 94(1):320\u2013323. https:\/\/doi.org\/10.1210\/jc.2008-1451","journal-title":"J Clin Endocrinol Metab Jan"},{"issue":"5","key":"1522_CR99","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1210\/en.2012-2070","volume":"154","author":"E Gentilin","year":"2013","unstructured":"Gentilin E, Tagliati F, Filieri C et al (2013) miR-26a plays an important role in cell cycle regulation in ACTH-secreting pituitary adenomas by modulating protein kinase C\u03b4. Endocrinol May 154(5):1690\u20131700. https:\/\/doi.org\/10.1210\/en.2012-2070","journal-title":"Endocrinol May"},{"issue":"1","key":"1522_CR100","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s12020-010-9346-0","volume":"38","author":"G Stilling","year":"2010","unstructured":"Stilling G, Sun Z, Zhang S et al (2010) MicroRNA expression in ACTH-producing pituitary tumors: up-regulation of microRNA-122 and\u2013\u2009493 in pituitary carcinomas. Endocr Aug 38(1):67\u201375. https:\/\/doi.org\/10.1007\/s12020-010-9346-0","journal-title":"Endocr Aug"},{"issue":"15","key":"1522_CR101","doi-asserted-by":"publisher","first-page":"10361","DOI":"10.1074\/jbc.M112.425504","volume":"12","author":"N Zhang","year":"2013","unstructured":"Zhang N, Lin JK, Chen J et al (2013) MicroRNA 375 mediates the signaling pathway of corticotropin-releasing factor (CRF) regulating pro-opiomelanocortin (POMC) expression by targeting mitogen-activated protein kinase 8. J Biol Chem Apr 12(15):10361\u201310373. https:\/\/doi.org\/10.1074\/jbc.M112.425504","journal-title":"J Biol Chem Apr"},{"issue":"1","key":"1522_CR102","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/ng.3166","volume":"47","author":"M Reincke","year":"2015","unstructured":"Reincke M, Sbiera S, Hayakawa A et al (2015) Mutations in the deubiquitinase gene USP8 cause Cushing\u2019s disease. Nat Genet Jan 47(1):31\u201338. https:\/\/doi.org\/10.1038\/ng.3166","journal-title":"Nat Genet Jan"},{"issue":"3","key":"1522_CR103","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/cr.2015.20","volume":"25","author":"ZY Ma","year":"2015","unstructured":"Ma ZY, Song ZJ, Chen JH et al (2015) Recurrent gain-of-function USP8 mutations in Cushing\u2019s disease. Cell Res Mar 25(3):306\u2013317. https:\/\/doi.org\/10.1038\/cr.2015.20","journal-title":"Cell Res Mar"},{"key":"1522_CR104","doi-asserted-by":"publisher","unstructured":"Bujko M, Kober P, Boresowicz J et al (2021) Differential MicroRNA expression in. J Clin Med Jan 20(3). https:\/\/doi.org\/10.3390\/jcm10030375","DOI":"10.3390\/jcm10030375"},{"issue":"12","key":"1522_CR105","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1080\/15592294.2019.1640546","volume":"12","author":"CL Miranda Furtado","year":"2019","unstructured":"Miranda Furtado CL, Dos Santos Luciano MC, Silva Santos RD, Furtado GP, Moraes MO, Pessoa C (2019) Epidrugs: targeting epigenetic marks in cancer treatment. Epigenetics 12(12):1164\u20131176. https:\/\/doi.org\/10.1080\/15592294.2019.1640546","journal-title":"Epigenetics"},{"issue":"3","key":"1522_CR106","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nm.2305","volume":"17","author":"M Rodr\u00edguez-Paredes","year":"2011","unstructured":"Rodr\u00edguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med Mar 17(3):330\u2013339. https:\/\/doi.org\/10.1038\/nm.2305","journal-title":"Nat Med Mar"},{"issue":"7","key":"1522_CR107","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1056\/NEJMra1805035","volume":"383","author":"SE Bates","year":"2020","unstructured":"Bates SE (2020) Epigenetic therapies for cancer. N Engl J Med Aug 383(7):650\u2013663. https:\/\/doi.org\/10.1056\/NEJMra1805035","journal-title":"N Engl J Med Aug"},{"issue":"8","key":"1522_CR108","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1093\/annonc\/mdn792","volume":"20","author":"L Stimson","year":"2009","unstructured":"Stimson L, Wood V, Khan O, Fotheringham S, La Thangue NB (2009) HDAC inhibitor-based therapies and haematological malignancy. Ann Oncol Aug 20(8):1293\u20131302. https:\/\/doi.org\/10.1093\/annonc\/mdn792","journal-title":"Ann Oncol Aug"},{"issue":"8","key":"1522_CR109","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.1210\/jc.2017-00464","volume":"08","author":"J Lu","year":"2017","unstructured":"Lu J, Chatain GP, Bugarini A et al (2017) Histone deacetylase inhibitor SAHA is a promising treatment of Cushing disease. J Clin Endocrinol Metab 08(8):2825\u20132835. https:\/\/doi.org\/10.1210\/jc.2017-00464","journal-title":"J Clin Endocrinol Metab"},{"issue":"18","key":"1522_CR110","doi-asserted-by":"publisher","first-page":"29558","DOI":"10.18632\/oncotarget.16365","volume":"8","author":"CT Ishida","year":"2017","unstructured":"Ishida CT, Bianchetti E, Shu C et al (2017) BH3-mimetics and BET-inhibitors elicit enhanced lethality in malignant glioma. Oncotarget May 8(18):29558\u201329573. https:\/\/doi.org\/10.18632\/oncotarget.16365","journal-title":"Oncotarget May"},{"issue":"38","key":"1522_CR111","doi-asserted-by":"publisher","first-page":"61469","DOI":"10.18632\/oncotarget.11129","volume":"7","author":"K Yamamoto","year":"2016","unstructured":"Yamamoto K, Tateishi K, Kudo Y et al (2016) Stromal remodeling by the BET bromodomain inhibitor JQ1 suppresses the progression of human pancreatic cancer. Oncotarget Sep 7(38):61469\u201361484. https:\/\/doi.org\/10.18632\/oncotarget.11129","journal-title":"Oncotarget Sep"},{"issue":"3","key":"1522_CR112","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1530\/ERC-19-0448","volume":"27","author":"KE Lines","year":"2020","unstructured":"Lines KE, Filippakopoulos P, Stevenson M et al (2020) Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells. Endocr Relat Cancer Mar 27(3):163\u2013174. https:\/\/doi.org\/10.1530\/ERC-19-0448","journal-title":"Endocr Relat Cancer Mar"},{"key":"1522_CR113","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s13148-016-0222-5","volume":"8","author":"L Altucci","year":"2016","unstructured":"Altucci L, Rots MG (2016) Epigenetic drugs: from chemistry via biology to medicine and back. Clin Epigenetics 8:56. https:\/\/doi.org\/10.1186\/s13148-016-0222-5","journal-title":"Clin Epigenetics"},{"issue":"2","key":"1522_CR114","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41571-019-0267-4","volume":"17","author":"D Morel","year":"2020","unstructured":"Morel D, Jeffery D, Aspeslagh S, Almouzni G, Postel-Vinay S (2020) Combining epigenetic drugs with other therapies for solid tumours - past lessons and future promise. Nat Rev Clin Oncol Feb 17(2):91\u2013107. https:\/\/doi.org\/10.1038\/s41571-019-0267-4","journal-title":"Nat Rev Clin Oncol Feb"},{"issue":"3","key":"1522_CR115","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s12022-021-09671-4","volume":"32","author":"O Mete","year":"2021","unstructured":"Mete O, Ezzat S, Perry A et al (2021) The pangenomic classification of pituitary neuroendocrine tumors: quality histopathology is required for accurate translational research. Endocr Pathol Sep 32(3):415\u2013417. https:\/\/doi.org\/10.1007\/s12022-021-09671-4","journal-title":"Endocr Pathol Sep"},{"key":"1522_CR116","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.mce.2018.01.020","volume":"15","author":"P Kober","year":"2018","unstructured":"Kober P, Boresowicz J, Rusetska N et al (2018) DNA methylation profiling in nonfunctioning pituitary adenomas. Mol Cell Endocrinol Sep 15:473:194\u2013204. https:\/\/doi.org\/10.1016\/j.mce.2018.01.020","journal-title":"Mol Cell Endocrinol Sep"},{"issue":"7697","key":"1522_CR117","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nature26000","volume":"22","author":"D Capper","year":"2018","unstructured":"Capper D, Jones DTW, Sill M et al (2018) DNA methylation-based classification of central nervous system tumours. Nat Mar 22(7697):469\u2013474. https:\/\/doi.org\/10.1038\/nature26000","journal-title":"Nat Mar"}],"container-title":["Pituitary"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11102-025-01522-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11102-025-01522-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11102-025-01522-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T19:21:01Z","timestamp":1751397661000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11102-025-01522-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,21]]},"references-count":117,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["1522"],"URL":"https:\/\/doi.org\/10.1007\/s11102-025-01522-3","relation":{},"ISSN":["1386-341X","1573-7403"],"issn-type":[{"value":"1386-341X","type":"print"},{"value":"1573-7403","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,21]]},"assertion":[{"value":"2 April 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"51"}}