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Analysis of Telomere Maintenance Related Genes Reveals NOP10 as a New Metastatic-Risk Marker in Pheochromocytoma/Paraganglioma.
Monteagudo, María; Martínez, Paula; Leandro-García, Luis J; Martínez-Montes, Ángel M; Calsina, Bruna; Pulgarín-Alfaro, Marta; Díaz-Talavera, Alberto; Mellid, Sara; Letón, Rocío; Gil, Eduardo; Pérez-Martínez, Manuel; Megías, Diego; Torres-Ruiz, Raúl; Rodriguez-Perales, Sandra; González, Patricia; Caleiras, Eduardo; Jiménez-Villa, Scherezade; Roncador, Giovanna; Álvarez-Escolá, Cristina; Regojo, Rita M; Calatayud, María; Guadalix, Sonsoles; Currás-Freixes, Maria; Rapizzi, Elena; Canu, Letizia; Nölting, Svenja; Remde, Hanna; Fassnacht, Martin; Bechmann, Nicole; Eisenhofer, Graeme; Mannelli, Massimo; Beuschlein, Felix; Quinkler, Marcus; Rodríguez-Antona, Cristina; Cascón, Alberto; Blasco, María A; Montero-Conde, Cristina; Robledo, Mercedes.
Affiliation
  • Monteagudo M; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Martínez P; PhD Program in Neuroscience, Autonoma de Madrid University, 28029 Madrid, Spain.
  • Leandro-García LJ; Telomeres and telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Martínez-Montes ÁM; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Calsina B; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Pulgarín-Alfaro M; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Díaz-Talavera A; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Mellid S; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Letón R; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain.
  • Gil E; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Pérez-Martínez M; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Megías D; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Torres-Ruiz R; Confocal Microscopy Core Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Rodriguez-Perales S; Confocal Microscopy Core Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • González P; Molecular Citogenetic, Unit Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Caleiras E; Molecular Citogenetic, Unit Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Jiménez-Villa S; Histopathology Core Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Roncador G; Histopathology Core Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Álvarez-Escolá C; Monoclonal Antibodies Core Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Regojo RM; Monoclonal Antibodies Core Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
  • Calatayud M; Department of Endocrinology, La Paz University Hospital, 28046 Madrid, Spain.
  • Guadalix S; Department of Pathology La Paz University Hospital, 28046 Madrid, Spain.
  • Currás-Freixes M; Department of Endocrinology, 12 de Octubre University Hospital, 28041 Madrid, Spain.
  • Rapizzi E; Department of Endocrinology, 12 de Octubre University Hospital, 28041 Madrid, Spain.
  • Canu L; Department of Endocrinology, Clínica Universidad de Navarra, 28027 Madrid, Spain.
  • Nölting S; Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.
  • Remde H; Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.
  • Fassnacht M; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.
  • Bechmann N; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, 97070 Würzburg, Germany.
  • Eisenhofer G; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, 97070 Würzburg, Germany.
  • Mannelli M; Comprehensive Cancer Center, Mainfranken University of Würzburg, 97070 Würzburg, Germany.
  • Beuschlein F; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01069 Dresden, Germany.
  • Quinkler M; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01069 Dresden, Germany.
  • Rodríguez-Antona C; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01069 Dresden, Germany.
  • Cascón A; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01069 Dresden, Germany.
  • Blasco MA; Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.
  • Montero-Conde C; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.
  • Robledo M; Klinik für Endokrinologie Diabetologie und Klinische Ernährung, Universitätsspital Zürich, 8091 Zürich, Switzerland.
Cancers (Basel) ; 13(19)2021 Sep 23.
Article in En | MEDLINE | ID: mdl-34638246
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Language: En Journal: Cancers (Basel) Year: 2021 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Language: En Journal: Cancers (Basel) Year: 2021 Document type: Article Affiliation country: