Analysis of telomere maintenance related genes reveals NOP10 as a new metastatic-risk marker in pheochromocytoma/paraganglioma

Please always quote using this URN: urn:nbn:de:bvb:20-opus-246321
  • One of the main problems we face with PPGL is the lack of molecular markers capable of predicting the development of metastases in patients. Telomere-related genes, such as TERT and ATRX, have been recently described in PPGL, supporting the association between the activation of immortalization mechanisms and disease progression. However, the contribution of other genes involving telomere preservation machinery has not been previously investigated. In this work, we aimed to analyze the prognostic value of a comprehensive set of genes involved inOne of the main problems we face with PPGL is the lack of molecular markers capable of predicting the development of metastases in patients. Telomere-related genes, such as TERT and ATRX, have been recently described in PPGL, supporting the association between the activation of immortalization mechanisms and disease progression. However, the contribution of other genes involving telomere preservation machinery has not been previously investigated. In this work, we aimed to analyze the prognostic value of a comprehensive set of genes involved in telomere maintenance. For this study, we collected 165 PPGL samples (97 non-metastatic/63 metastatic), genetically characterized, in which the expression of 29 genes of interest was studied by NGS. Three of the 29 genes studied, TERT, ATRX and NOP10, showed differential expression between metastatic and non-metastatic cases, and alterations in these genes were associated with a shorter time to progression, independent of SDHB-status. We studied telomere length by Q-FISH in patient samples and in an in vitro model. NOP10 overexpressing tumors displayed an intermediate-length telomere phenotype without ALT, and in vitro results suggest that NOP10 has a role in telomerase-dependent telomere maintenance. We also propose the implementation of NOP10 IHC to better stratify PPGL patients.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: María Monteagudo, Paula Martínez, Luis J. Leandro-García, Ángel M. Martínez-Montes, Bruna Calsina, Marta Pulgarín-Alfaro, Alberto Díaz-Talavera, Sara Mellid, Rocío Letón, Eduardo Gil, Manuel Pérez-Martínez, Diego Megías, Raúl Torres-Ruiz, Sandra Rodriguez-Perales, Patricia González, Eduardo Caleiras, Scherezade Jiménez-Villa, Giovanna Roncador, Cristina Álvarez-Escolá, Rita M. Regojo, María Calatayud, Sonsoles Guadalix, Maria Currás-Freixes, Elena Rapizzi, Letizia Canu, Svenja Nölting, Hanna Remde, Martin Fassnacht, Nicole Bechmann, Graeme Eisenhofer, Massimo Mannelli, Felix Beuschlein, Marcus Quinkler, Cristina Rodríguez-Antona, Alberto Cascón, María A. Blasco, Cristina Montero-Conde, Mercedes Robledo
URN:urn:nbn:de:bvb:20-opus-246321
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik I
Medizinische Fakultät / Comprehensive Cancer Center Mainfranken
Language:English
Parent Title (English):Cancers
ISSN:2072-6694
Year of Completion:2021
Volume:13
Issue:19
Article Number:4758
Source:Cancers (2021) 13:19, 4758. https://doi.org/10.3390/cancers13194758
DOI:https://doi.org/10.3390/cancers13194758
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:ALT; ATRX; NOP10; PPGL; TERT; paraganglioma; pheochromocytoma; prognostic biomarker; telomeres
Release Date:2023/05/25
Date of first Publication:2021/09/23
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International