ECE2018 Guided Posters Pituitary Basic (8 abstracts)
Prominent expression of MAX and MEG3, despite lack of mutations in MAX, suggest a potential role for 14q genes in pituitary adenomas
Alejandro Ibáñez-Costa 1, , Rocío Letón 5 , Esther Rivero-Cortés 1, , Cristina Álvarez-Escolá 6 , Paloma Rodriguez Poyo-Guerrero 7 , Inmaculada Gavilán-Villarejo 8 , Márta Korbonits 9 , Mónica Marazuela 10 , María Ángeles Gálvez-Moreno 1, , Alfonso Soto-Moreno 12 , Mercedes Robledo 5, , Justo P Castaño 1, & Raúl M Luque 1,
1Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain; 2Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain; 3Reina Sofia University Hospital (HURS), Cordoba, Spain; 4Biomedical Research Networking Center on Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain; 5Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain; 6Service of Endocrinology, Hospital Universitario La Paz, Madrid, Spain; 7Service of Endocrinology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 8Endocrinology and Nutrition Unit, Hospital Universitario Puerta del Mar, Cadiz, Spain; 9Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 10Department of Endocrinology and Nutrition, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid, Spain; 11Service of Endocrinology and Nutrition, Cordoba, Spain; 12Metabolism and Nutrition Unit, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain; 13Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERer), Madrid, Spain.
Pituitary adenomas (PA), as well as pheochromocytomas and paragangliomas, are neuroendocrine tumors that arise from cells derived from the pituitary, adrenal and extra-adrenal nervous system, respectively. Recent studies have identified a growing series of susceptibility genes for these pathologies. Some genes may be associated with the development of both types of pathologies, as it is the case for succinate dehydrogenase complex genes, while, PAs have not been reported to date in patients harboring the most recently discovered pheochromocytomas and paraganglioma susceptibility genes, such as MAX, the MYC-associated factor X gene. Interestingly MAX is able to form heterodimers with MYC, an oncogene implicated in cell proliferation and apoptosis, which has been recently identified as a biomarker of aggressiveness in non-functioning Pas (NFPAs). Thus, to explore if MAX and/or MEG3 (an imprinted gene located close to MAX, which arose as a marker of uniparental disomy in MAX-mutated patients) are associated with pituitary tumorigenesis, we analyzed MAX genomic sequence [by denaturing high-performance liquid chromatography (dHPLC)] in a cohort of 141 PA samples [71 NFPAs, 40 somatotropinomas, 19 corticotropinomas, 10 prolactinomas and 1 gonadotropinoma], together with the analysis of MAX and MEG3 expression (by qPCR) and/or methylation status (using bisulfite modification and methylation specific PCR). These analyses revealed that MAX and MEG3 were substantially expressed in the different types of PA, wherein they displayed a tumor type-specific expression pattern: expression levels were significantly higher in somatotropinomas compared with NFPAs. Specifically, detectable MAX and MEG3 expression levels was present in 100% and 97% of somatotropinomas, 93% and 81% of NFPAs, 90% of corticotropinomas, and in 60% and 100% of prolactinomas, respectively and both were expressed in the gonadotropinoma. Interestingly, MAX and MEG3 expression levels were directly correlated in this cohort of PAs, an observation that also tended to arise independently in somatotropinomas and NFPAs (p=0.07 and 0.08, respectively). Remarkably, none of the PA samples presented MAX mutations in dHPLC and sequencing analyses, nor displayed significant alterations in the methylation status of the CpG sites of MAX and MEG3 genes examined. Altogether, our results show that mutations in MAX gene do not seem to play a relevant role in pituitary tumorigenesis in this cohort of patients. However, MAX and MEG3 are significantly expressed, suggesting that the study of their functional role in pituitary pathophysiology could represent an interesting avenue for the identification of novel biomarkers and/or therapeutic targets in these pathologies.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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