TY  - JOUR
A1  - Canu, Letizia
A1  - Puglisi, Soraya
A1  - Berchialla, Paola
A1  - De Filpo, Giuseppina
A1  - Brignardello, Francesca
A1  - Schiavi, Francesca
A1  - Ferrara, Alfonso Massimiliano
A1  - Zovato, Stefania
A1  - Luconi, Michaela
A1  - Pia, Anna
A1  - Appetecchia, Marialuisa
A1  - Arvat, Emanuela
A1  - Letizia, Claudio
A1  - Maccario, Mauro
A1  - Parasiliti-Caprino, Mirko
A1  - Altieri, Barbara
A1  - Faggiano, Antongiulio
A1  - Modica, Roberta
A1  - Morelli, Valentina
A1  - Arosio, Maura
A1  - Verga, Uberta
A1  - Pellegrino, Micaela
A1  - Petramala, Luigi
A1  - Concistrè, Antonio
A1  - Razzore, Paola
A1  - Ercolino, Tonino
A1  - Rapizzi, Elena
A1  - Maggi, Mario
A1  - Stigliano, Antonio
A1  - Burrello, Jacopo
A1  - Terzolo, Massimo
A1  - Opocher, Giuseppe
A1  - Mannelli, Massimo
A1  - Reimondo, Giuseppe
T1  - A multicenter epidemiological study on second malignancy in non-syndromic pheochromocytoma/paraganglioma patients in Italy
JF  - Cancers
N2  - No studies have carried out an extensive analysis of the possible association between non-syndromic pheochromocytomas and paragangliomas (PPGLs) and other malignancies. To assess >the risk of additional malignancy in PPGL, we retrospectively evaluated 741 patients with PPGLs followed-up in twelve referral centers in Italy. Incidence of second malignant tumors was compared between this cohort and Italian patients with two subsequent malignancies. Among our patients, 95 (12.8%) developed a second malignant tumor, which were mainly prostate, colorectal and lung/bronchial cancers in males, breast cancer, differentiated thyroid cancer and melanoma in females. The standardized incidence ratio was 9.59 (95% CI 5.46–15.71) in males and 13.21 (95% CI 7.52–21.63) in females. At multivariable analysis, the risk of developing a second malignant tumor increased with age at diagnosis (HR 2.50, 95% CI 1.15–5.44, p = 0.021 for 50–59 vs. <50-year category; HR 3.46, 95% CI 1.67–7.15, p < 0.001 for >60- vs. <50-year). In patients with available genetic evaluation, a positive genetic test was inversely associated with the risk of developing a second tumor (HR 0.25, 95% CI 0.10–0.63, p = 0.003). In conclusion, PPGLs patients have higher incidence of additional malignant tumors compared to the general population who had a first malignancy, which could have an impact on the surveillance strategy.
KW  - pheochromocytoma
KW  - paraganglioma
KW  - epidemiology
KW  - genetic analysis
KW  - mortality
KW  - surveillance
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250148
SN  - 2072-6694
VL  - 13
IS  - 22
ER  - 
TY  - JOUR
A1  - Monteagudo, María
A1  - Martínez, Paula
A1  - Leandro-García, Luis J.
A1  - Martínez-Montes, Ángel M.
A1  - Calsina, Bruna
A1  - Pulgarín-Alfaro, Marta
A1  - Díaz-Talavera, Alberto
A1  - Mellid, Sara
A1  - Letón, Rocío
A1  - Gil, Eduardo
A1  - Pérez-Martínez, Manuel
A1  - Megías, Diego
A1  - Torres-Ruiz, Raúl
A1  - Rodriguez-Perales, Sandra
A1  - González, Patricia
A1  - Caleiras, Eduardo
A1  - Jiménez-Villa, Scherezade
A1  - Roncador, Giovanna
A1  - Álvarez-Escolá, Cristina
A1  - Regojo, Rita M.
A1  - Calatayud, María
A1  - Guadalix, Sonsoles
A1  - Currás-Freixes, Maria
A1  - Rapizzi, Elena
A1  - Canu, Letizia
A1  - Nölting, Svenja
A1  - Remde, Hanna
A1  - Fassnacht, Martin
A1  - Bechmann, Nicole
A1  - Eisenhofer, Graeme
A1  - Mannelli, Massimo
A1  - Beuschlein, Felix
A1  - Quinkler, Marcus
A1  - Rodríguez-Antona, Cristina
A1  - Cascón, Alberto
A1  - Blasco, María A.
A1  - Montero-Conde, Cristina
A1  - Robledo, Mercedes
T1  - Analysis of telomere maintenance related genes reveals NOP10 as a new metastatic-risk marker in pheochromocytoma/paraganglioma
JF  - Cancers
N2  - 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.
KW  - pheochromocytoma
KW  - paraganglioma
KW  - PPGL
KW  - telomeres
KW  - prognostic biomarker
KW  - ALT
KW  - TERT
KW  - ATRX
KW  - NOP10
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246321
SN  - 2072-6694
VL  - 13
IS  - 19
ER  -