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Endocrine Abstracts (2019) 63 P711 | DOI: 10.1530/endoabs.63.P711

ECE2019 Poster Presentations Pituitary and Neuroendocrinology 2 (70 abstracts)

Whole genome demethylation status of somatic DNA extracted from different pituitary adenoma types

Borbála Szabó 1 , Kinga Németh 2 , Katalin Mészáros 2, , Nikolett Szücs 1 , Sándor Czirják 4 , Lilla Reiniger 5 , Attila Patócs 2, & Henriett Butz 2,

12nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary; 2Momentum Hereditary Endocrine Tumors Research Group, Budapest, Hungary; 3National Bionics Program, Semmelweis University, Budapest, Hungary; 4National Institute of Clinical Neurosciences, Budapest, Hungary; 51st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; 6Department of Laboratory Medicine, Semmelweis University, Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary.

Background: Although the role of hypermethylation of certain tumor suppressor genes are known in pituitary adenomas little information is available regarding whole methylation-demethylation status and especially regarding its correlation with clinical parameters. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) is an easy and accurate method to detect the level of methylcytosine (5 mC) and the demethylation intermedier hydroxymethylcytosine (5 hmC) too.

Material and methods: Overall, 44 fresh frozen pituitary adenoma tissues (29 gonadotroph, 12 somatotroph, 3 corticotroph). were collected and categorized according to the 2017 WHO classification After DNA extraction cytosine (C)%, 5mC% and 5 hmC% and (5 hmC/5 mC)*100) ratios were determined by HPLC-MS/MS system. Results were correlated with clinicopathological parameters.

Results: Higher level of 5hmC% and 5hmC%/5mC% ratio was confirmed in hormone-negative (HN) HN-SF1+ and HN-Tpit+ groups compared to FSH/LH+ and GH secreting adenomas. Significant difference between HN-SF1+ gonadotroph and FSH/LH+ gonadotroph adenomas was found but there was no alteration between HN-SF1+ and HN-Tpit+ tumors. In samples with higher proliferative index (Ki-67>4% vs 1–2% or 3–4%) significantly lower 5 hmC% and 5hmC%/5mC% were detected regardless of tumor type (P=0.009). However, after dissecting histological groups this phenomenon was most characteristic of GH+ and HN adenomas and it was absent in FSH/LH+ adenomas (by two-way ANOVA both Ki-67 and histological group factors reached significance levels (P=0.003 and P=0.029, respectively)).

Conclusion: 5hmC% and 5hmC/5mC ratio indicating demethylation status can be reliably detected by HPLC-MS-MS method in somatic DNA extracted from pituitary adenomas. HN adenomas show increased demethylation compared to FSH/LH+ and GH+ adenomas independently from their transcription factor status. Adenomas with higher Ki-67 indexes exhibit gradually lower demethylation. 5 hmC/5 mC ratio may be used as prognostic tissue biomarker but these data need to be further investigated on higher sample set.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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