DNA Methylation of Tumor Suppressor Genes in Pituitary Neuroendocrine Tumors
Please use this identifier to cite or link to this item:
http://hdl.handle.net/10045/98758
Title: | DNA Methylation of Tumor Suppressor Genes in Pituitary Neuroendocrine Tumors |
---|---|
Authors: | Garcia-Martinez, Araceli | Sottile, Johana | Sánchez-Tejada, Laura | Fajardo, Carmen | Cámara, Rosa | Lamas, Cristina | Barberá, Víctor Manuel | Picó, Antonio |
Research Group/s: | Transducción de Señales en Bacterias |
Center, Department or Service: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Keywords: | DNA methylation | Tumor suppressor genes | Pituitary neuroendocrine tumors |
Knowledge Area: | Genética |
Issue Date: | Apr-2019 |
Publisher: | Oxford University Press |
Citation: | The Journal of Clinical Endocrinology & Metabolism. 2019, 104(4): 1272-1282. doi:10.1210/jc.2018-01856 |
Abstract: | Context: Epigenetic alterations may play a role in the development and behavior of pituitary neuroendocrine tumors (PitNETs). Objective: To evaluate the effect of methylation of tumor suppressor genes (TSGs) on their gene expression and on the behavior of PitNETs. Material and Methods: We used methylation-specific multiplex ligation-dependent probe amplification and quantitative real-time PCR techniques to analyze the DNA-promoter hypermethylation and gene expression of 35 TSGs in 105 PitNETs. We defined functionality, size, and invasiveness of tumors according to their clinical manifestations, Hardy’s classification, and MRI invasiveness of the cavernous sinus, respectively. Results: We observed different methylation patterns among PitNET subtypes. The methylation status of TP73 correlated negatively with its gene expression in the overall series (P = 0.013) and in some subtypes. MSH6 and CADM1 showed higher methylation frequency in macroadenomas than in microadenomas in the overall series and in corticotroph PitNETs (all P ≤ 0.053). ESR1 and RASSF1 were more highly methylated in noninvasive than in invasive tumors in the overall series (P = 0.054 and P = 0.031, respectively) and in the gonadotroph subtype (P = 0.055 and P = 0.050, respectively). ESR1 and CASP8 appeared more hypermethylated in functioning than in silent corticotroph tumors (P = 0.034 and P = 0.034, respectively). Conclusions: DNA methylation of TSGs has a selective effect on their gene expression and on the growth and invasiveness of PitNETs. Its involvement in their functionality is biased because all silent operated tumors are macroadenomas, whereas all operated microadenomas are functioning ones. Therefore, the subtypes of PitNETs should be considered different entities. |
Sponsor: | This work was funded by Novartis Oncology (to A.P.). |
URI: | http://hdl.handle.net/10045/98758 |
ISSN: | 0021-972X (Print) | 1945-7197 (Online) |
DOI: | 10.1210/jc.2018-01856 |
Language: | eng |
Type: | info:eu-repo/semantics/article |
Rights: | © 2019 Endocrine Society |
Peer Review: | si |
Publisher version: | https://doi.org/10.1210/jc.2018-01856 |
Appears in Collections: | INV - TSB - Artículos de Revistas |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
2019_Garcia-Martinez_etal_JClinEndocrinolMetab_final.pdf | Versión final (acceso restringido) | 539,21 kB | Adobe PDF | Open Request a copy |
Items in RUA are protected by copyright, with all rights reserved, unless otherwise indicated.