Scientific publications
Analysis of Telomere Maintenance Related Genes Reveals NOP10 as a New Metastatic-Risk Marker in Pheochromocytoma/Paraganglioma
María Monteagudo 1 2 , Paula Martínez 3 , Luis J Leandro-García 1 , Ángel M Martínez-Montes 1 , Bruna Calsina 1 , Marta Pulgarín-Alfaro 1 , Alberto Díaz-Talavera 1 4 , Sara Mellid 1 , Rocío Letón 1 , Eduardo Gil 1 , Manuel Pérez-Martínez 5 , Diego Megías 5 , Raúl Torres-Ruiz 6 , Sandra Rodriguez-Perales 6 , Patricia González 7 , Eduardo Caleiras 7 , Scherezade Jiménez-Villa 8 , Giovanna Roncador 8 , Cristina Álvarez-Escolá 9 , Rita M Regojo 10 , María Calatayud 11 , Sonsoles Guadalix 11 , Maria Currás-Freixes 12 , Elena Rapizzi 13 , Letizia Canu 13 , Svenja Nölting 14 , Hanna Remde 15 , Martin Fassnacht 15 16 , Nicole Bechmann 17 18 , Graeme Eisenhofer 17 18 , Massimo Mannelli 13 , Felix Beuschlein 14 19 , Marcus Quinkler 20 , Cristina Rodríguez-Antona 1 4 , Alberto Cascón 1 4 , María A Blasco 3 , Cristina Montero-Conde 1 4 , Mercedes Robledo 1 4
Abstract
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 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.
CITATION Cancers (Basel). 2021 Sep 23;13(19):4758. doi: 10.3390/cancers13194758