Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers

Montero-Conde, C. (Cristina)|||/items/6d47bc2d-9ef9-4bfd-b374-e423d15b1a25; Leandro-García, L.J. (Luis J.)|||/items/2b44a058-b84c-4a11-ba79-586cd96d0448; Martínez-Montes, A.M. (Ángel M.)|||/items/b516ac80-4289-4500-bf8d-6020481456a1; Martínez, P. (Paula)|||/items/1d9dee42-36b1-44e9-bbe7-6998383a3bf5; Moya-Faz, F.J. (Francisco José)|||/items/6102aa74-fb85-4e24-a56b-0d455483b283; Leton, R. (Rocío)|||/items/292ea14e-4a9d-44f5-b173-d1a1285e3e25; Gil, E. (Eduardo)|||/items/b4f29bae-0e0f-4bd2-a246-99578b4855ac; Martínez-Puente, N. (Natalia)|||/items/342fc39d-2ebf-41dd-beb9-a9bd4ebea359; Guadalix, S. (Sonsoles)|||/items/59ca9666-3549-43be-b944-428d56084e83; Currás, M. (María)|||/items/da704e52-e034-47bd-9844-b7ce28b1ef2f; Garcia-Tobar, L. (Laura)|||/items/64b398ed-0d60-4773-9118-e862d5d28ff9; Zafón, C. (Carles)|||/items/25a3e6e5-617d-4937-b3ce-7fed784dbb47; Jordá, M. (Mireia)|||/items/3d80cad9-83d9-4ca7-bce9-327e348710c2; Riesco-Eizaguirre, G. (Garcilaso)|||/items/5b966126-3180-4b86-8215-aa6793d1b0d7; García-Montón-González P. (Patricia)|||/items/066b96d4-7696-4d42-8723-7c86875ee1bf; Monteagudo, M. (María)|||/items/13516cb2-250f-4738-961c-d101f67477d7; Torres-Pérez, R. (Rafael)|||/items/a5a8b84f-5a87-4563-8114-2d402eea8f95; Mancikova, V. (Veronika)|||/items/286402de-9eee-4e42-b39a-4ff976fe6d36; Ruiz-Llorente, S. (Sergio)|||/items/94866d6e-caf0-4040-b178-c6702425da61; Martínez-Pérez, J.M. (José Manuel)|||/items/5227974d-c5c8-45d6-a1de-3985e5732b27; Pita, G. (Guillermo)|||/items/511d3d5b-17c7-49eb-99a2-b5e30c36b145; Galofre-Ferrater, J.C. (Juan Carlos)|||/items/e7463ff9-97f4-4119-a307-fd978c0017fd; Gonzalez-Neira, A. (Anna)|||/items/8595341c-963a-4cbe-bdec-8b5267ad1b73; Cascon, A. (Alberto)|||/items/15e22b8d-8e23-4935-a21e-1796f757fa76; Rodriguez-Antona, C. (Cristina)|||/items/7e878c35-4151-4360-800d-066cc7de6740; Megías, D. (Diego)|||/items/d96eda06-62b0-485e-8275-245da5f19ebd; Blasco, M.A. (Maria A.)|||/items/947c369b-148a-4b1e-b1d0-33d7ed216c19; Caleiras, E. (Eduardo)|||/items/a50fa3bb-6348-4b3b-996d-a6bb73dcdd8c; Rodriguez-Perales, S. (Sandra)|||/items/00d786b0-c4eb-4585-8b7a-30c17f7a74af; Robledo, M. (Mercedes)|||/items/3fa84b0c-f9be-49a8-9290-c1c74231ac11

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers

Background: Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer. Methods and results: In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours...

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Detalles Bibliográficos
Autores:	Montero-Conde, C. (Cristina)\|\|\|/items/6d47bc2d-9ef9-4bfd-b374-e423d15b1a25, Leandro-García, L.J. (Luis J.)\|\|\|/items/2b44a058-b84c-4a11-ba79-586cd96d0448, Martínez-Montes, A.M. (Ángel M.)\|\|\|/items/b516ac80-4289-4500-bf8d-6020481456a1, Martínez, P. (Paula)\|\|\|/items/1d9dee42-36b1-44e9-bbe7-6998383a3bf5, Moya-Faz, F.J. (Francisco José)\|\|\|/items/6102aa74-fb85-4e24-a56b-0d455483b283, Leton, R. (Rocío)\|\|\|/items/292ea14e-4a9d-44f5-b173-d1a1285e3e25, Gil, E. (Eduardo)\|\|\|/items/b4f29bae-0e0f-4bd2-a246-99578b4855ac, Martínez-Puente, N. (Natalia)\|\|\|/items/342fc39d-2ebf-41dd-beb9-a9bd4ebea359, Guadalix, S. (Sonsoles)\|\|\|/items/59ca9666-3549-43be-b944-428d56084e83, Currás, M. (María)\|\|\|/items/da704e52-e034-47bd-9844-b7ce28b1ef2f, Garcia-Tobar, L. (Laura)\|\|\|/items/64b398ed-0d60-4773-9118-e862d5d28ff9, Zafón, C. (Carles)\|\|\|/items/25a3e6e5-617d-4937-b3ce-7fed784dbb47, Jordá, M. (Mireia)\|\|\|/items/3d80cad9-83d9-4ca7-bce9-327e348710c2, Riesco-Eizaguirre, G. (Garcilaso)\|\|\|/items/5b966126-3180-4b86-8215-aa6793d1b0d7, García-Montón-González P. (Patricia)\|\|\|/items/066b96d4-7696-4d42-8723-7c86875ee1bf, Monteagudo, M. (María)\|\|\|/items/13516cb2-250f-4738-961c-d101f67477d7, Torres-Pérez, R. (Rafael)\|\|\|/items/a5a8b84f-5a87-4563-8114-2d402eea8f95, Mancikova, V. (Veronika)\|\|\|/items/286402de-9eee-4e42-b39a-4ff976fe6d36, Ruiz-Llorente, S. (Sergio)\|\|\|/items/94866d6e-caf0-4040-b178-c6702425da61, Martínez-Pérez, J.M. (José Manuel)\|\|\|/items/5227974d-c5c8-45d6-a1de-3985e5732b27, Pita, G. (Guillermo)\|\|\|/items/511d3d5b-17c7-49eb-99a2-b5e30c36b145, Galofre-Ferrater, J.C. (Juan Carlos)\|\|\|/items/e7463ff9-97f4-4119-a307-fd978c0017fd, Gonzalez-Neira, A. (Anna)\|\|\|/items/8595341c-963a-4cbe-bdec-8b5267ad1b73, Cascon, A. (Alberto)\|\|\|/items/15e22b8d-8e23-4935-a21e-1796f757fa76, Rodriguez-Antona, C. (Cristina)\|\|\|/items/7e878c35-4151-4360-800d-066cc7de6740, Megías, D. (Diego)\|\|\|/items/d96eda06-62b0-485e-8275-245da5f19ebd, Blasco, M.A. (Maria A.)\|\|\|/items/947c369b-148a-4b1e-b1d0-33d7ed216c19, Caleiras, E. (Eduardo)\|\|\|/items/a50fa3bb-6348-4b3b-996d-a6bb73dcdd8c, Rodriguez-Perales, S. (Sandra)\|\|\|/items/00d786b0-c4eb-4585-8b7a-30c17f7a74af, Robledo, M. (Mercedes)\|\|\|/items/3fa84b0c-f9be-49a8-9290-c1c74231ac11
Tipo de recurso:	artículo
Fecha de publicación:	2022
País:	España
Institución:	Universidad de Navarra
Repositorio:	Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:	inglés
OAI Identifier:	oai:dadun.unav.edu:10171/122440
Acceso en línea:	https://hdl.handle.net/10171/122440
Access Level:	acceso abierto
Palabra clave:	5p-end FISH TERC TERT promoter methylation TERT promoter mutation Subtelomeric gene expression Telomere shortening

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oai_identifier_str	oai:dadun.unav.edu:10171/122440
network_acronym_str	ES
network_name_str	España
repository_id_str
dc.title.none.fl_str_mv	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers
title	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers
spellingShingle	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers Montero-Conde, C. (Cristina)\|\|\|/items/6d47bc2d-9ef9-4bfd-b374-e423d15b1a25 5p-end FISH TERC TERT promoter methylation TERT promoter mutation Subtelomeric gene expression Telomere shortening
title_short	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers
title_full	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers
title_fullStr	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers
title_full_unstemmed	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers
title_sort	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers
dc.creator.none.fl_str_mv	Montero-Conde, C. (Cristina)\|\|\|/items/6d47bc2d-9ef9-4bfd-b374-e423d15b1a25 Leandro-García, L.J. (Luis J.)\|\|\|/items/2b44a058-b84c-4a11-ba79-586cd96d0448 Martínez-Montes, A.M. (Ángel M.)\|\|\|/items/b516ac80-4289-4500-bf8d-6020481456a1 Martínez, P. (Paula)\|\|\|/items/1d9dee42-36b1-44e9-bbe7-6998383a3bf5 Moya-Faz, F.J. (Francisco José)\|\|\|/items/6102aa74-fb85-4e24-a56b-0d455483b283 Leton, R. (Rocío)\|\|\|/items/292ea14e-4a9d-44f5-b173-d1a1285e3e25 Gil, E. (Eduardo)\|\|\|/items/b4f29bae-0e0f-4bd2-a246-99578b4855ac Martínez-Puente, N. (Natalia)\|\|\|/items/342fc39d-2ebf-41dd-beb9-a9bd4ebea359 Guadalix, S. (Sonsoles)\|\|\|/items/59ca9666-3549-43be-b944-428d56084e83 Currás, M. (María)\|\|\|/items/da704e52-e034-47bd-9844-b7ce28b1ef2f Garcia-Tobar, L. (Laura)\|\|\|/items/64b398ed-0d60-4773-9118-e862d5d28ff9 Zafón, C. (Carles)\|\|\|/items/25a3e6e5-617d-4937-b3ce-7fed784dbb47 Jordá, M. (Mireia)\|\|\|/items/3d80cad9-83d9-4ca7-bce9-327e348710c2 Riesco-Eizaguirre, G. (Garcilaso)\|\|\|/items/5b966126-3180-4b86-8215-aa6793d1b0d7 García-Montón-González P. (Patricia)\|\|\|/items/066b96d4-7696-4d42-8723-7c86875ee1bf Monteagudo, M. (María)\|\|\|/items/13516cb2-250f-4738-961c-d101f67477d7 Torres-Pérez, R. (Rafael)\|\|\|/items/a5a8b84f-5a87-4563-8114-2d402eea8f95 Mancikova, V. (Veronika)\|\|\|/items/286402de-9eee-4e42-b39a-4ff976fe6d36 Ruiz-Llorente, S. (Sergio)\|\|\|/items/94866d6e-caf0-4040-b178-c6702425da61 Martínez-Pérez, J.M. (José Manuel)\|\|\|/items/5227974d-c5c8-45d6-a1de-3985e5732b27 Pita, G. (Guillermo)\|\|\|/items/511d3d5b-17c7-49eb-99a2-b5e30c36b145 Galofre-Ferrater, J.C. (Juan Carlos)\|\|\|/items/e7463ff9-97f4-4119-a307-fd978c0017fd Gonzalez-Neira, A. (Anna)\|\|\|/items/8595341c-963a-4cbe-bdec-8b5267ad1b73 Cascon, A. (Alberto)\|\|\|/items/15e22b8d-8e23-4935-a21e-1796f757fa76 Rodriguez-Antona, C. (Cristina)\|\|\|/items/7e878c35-4151-4360-800d-066cc7de6740 Megías, D. (Diego)\|\|\|/items/d96eda06-62b0-485e-8275-245da5f19ebd Blasco, M.A. (Maria A.)\|\|\|/items/947c369b-148a-4b1e-b1d0-33d7ed216c19 Caleiras, E. (Eduardo)\|\|\|/items/a50fa3bb-6348-4b3b-996d-a6bb73dcdd8c Rodriguez-Perales, S. (Sandra)\|\|\|/items/00d786b0-c4eb-4585-8b7a-30c17f7a74af Robledo, M. (Mercedes)\|\|\|/items/3fa84b0c-f9be-49a8-9290-c1c74231ac11
author	Montero-Conde, C. (Cristina)\|\|\|/items/6d47bc2d-9ef9-4bfd-b374-e423d15b1a25
author_facet	Montero-Conde, C. (Cristina)\|\|\|/items/6d47bc2d-9ef9-4bfd-b374-e423d15b1a25 Leandro-García, L.J. (Luis J.)\|\|\|/items/2b44a058-b84c-4a11-ba79-586cd96d0448 Martínez-Montes, A.M. (Ángel M.)\|\|\|/items/b516ac80-4289-4500-bf8d-6020481456a1 Martínez, P. (Paula)\|\|\|/items/1d9dee42-36b1-44e9-bbe7-6998383a3bf5 Moya-Faz, F.J. (Francisco José)\|\|\|/items/6102aa74-fb85-4e24-a56b-0d455483b283 Leton, R. (Rocío)\|\|\|/items/292ea14e-4a9d-44f5-b173-d1a1285e3e25 Gil, E. (Eduardo)\|\|\|/items/b4f29bae-0e0f-4bd2-a246-99578b4855ac Martínez-Puente, N. (Natalia)\|\|\|/items/342fc39d-2ebf-41dd-beb9-a9bd4ebea359 Guadalix, S. (Sonsoles)\|\|\|/items/59ca9666-3549-43be-b944-428d56084e83 Currás, M. (María)\|\|\|/items/da704e52-e034-47bd-9844-b7ce28b1ef2f Garcia-Tobar, L. (Laura)\|\|\|/items/64b398ed-0d60-4773-9118-e862d5d28ff9 Zafón, C. (Carles)\|\|\|/items/25a3e6e5-617d-4937-b3ce-7fed784dbb47 Jordá, M. (Mireia)\|\|\|/items/3d80cad9-83d9-4ca7-bce9-327e348710c2 Riesco-Eizaguirre, G. (Garcilaso)\|\|\|/items/5b966126-3180-4b86-8215-aa6793d1b0d7 García-Montón-González P. (Patricia)\|\|\|/items/066b96d4-7696-4d42-8723-7c86875ee1bf Monteagudo, M. (María)\|\|\|/items/13516cb2-250f-4738-961c-d101f67477d7 Torres-Pérez, R. (Rafael)\|\|\|/items/a5a8b84f-5a87-4563-8114-2d402eea8f95 Mancikova, V. (Veronika)\|\|\|/items/286402de-9eee-4e42-b39a-4ff976fe6d36 Ruiz-Llorente, S. (Sergio)\|\|\|/items/94866d6e-caf0-4040-b178-c6702425da61 Martínez-Pérez, J.M. (José Manuel)\|\|\|/items/5227974d-c5c8-45d6-a1de-3985e5732b27 Pita, G. (Guillermo)\|\|\|/items/511d3d5b-17c7-49eb-99a2-b5e30c36b145 Galofre-Ferrater, J.C. (Juan Carlos)\|\|\|/items/e7463ff9-97f4-4119-a307-fd978c0017fd Gonzalez-Neira, A. (Anna)\|\|\|/items/8595341c-963a-4cbe-bdec-8b5267ad1b73 Cascon, A. (Alberto)\|\|\|/items/15e22b8d-8e23-4935-a21e-1796f757fa76 Rodriguez-Antona, C. (Cristina)\|\|\|/items/7e878c35-4151-4360-800d-066cc7de6740 Megías, D. (Diego)\|\|\|/items/d96eda06-62b0-485e-8275-245da5f19ebd Blasco, M.A. (Maria A.)\|\|\|/items/947c369b-148a-4b1e-b1d0-33d7ed216c19 Caleiras, E. (Eduardo)\|\|\|/items/a50fa3bb-6348-4b3b-996d-a6bb73dcdd8c Rodriguez-Perales, S. (Sandra)\|\|\|/items/00d786b0-c4eb-4585-8b7a-30c17f7a74af Robledo, M. (Mercedes)\|\|\|/items/3fa84b0c-f9be-49a8-9290-c1c74231ac11
author_role	author
author2	Leandro-García, L.J. (Luis J.)\|\|\|/items/2b44a058-b84c-4a11-ba79-586cd96d0448 Martínez-Montes, A.M. (Ángel M.)\|\|\|/items/b516ac80-4289-4500-bf8d-6020481456a1 Martínez, P. (Paula)\|\|\|/items/1d9dee42-36b1-44e9-bbe7-6998383a3bf5 Moya-Faz, F.J. (Francisco José)\|\|\|/items/6102aa74-fb85-4e24-a56b-0d455483b283 Leton, R. (Rocío)\|\|\|/items/292ea14e-4a9d-44f5-b173-d1a1285e3e25 Gil, E. (Eduardo)\|\|\|/items/b4f29bae-0e0f-4bd2-a246-99578b4855ac Martínez-Puente, N. (Natalia)\|\|\|/items/342fc39d-2ebf-41dd-beb9-a9bd4ebea359 Guadalix, S. (Sonsoles)\|\|\|/items/59ca9666-3549-43be-b944-428d56084e83 Currás, M. (María)\|\|\|/items/da704e52-e034-47bd-9844-b7ce28b1ef2f Garcia-Tobar, L. (Laura)\|\|\|/items/64b398ed-0d60-4773-9118-e862d5d28ff9 Zafón, C. (Carles)\|\|\|/items/25a3e6e5-617d-4937-b3ce-7fed784dbb47 Jordá, M. (Mireia)\|\|\|/items/3d80cad9-83d9-4ca7-bce9-327e348710c2 Riesco-Eizaguirre, G. (Garcilaso)\|\|\|/items/5b966126-3180-4b86-8215-aa6793d1b0d7 García-Montón-González P. (Patricia)\|\|\|/items/066b96d4-7696-4d42-8723-7c86875ee1bf Monteagudo, M. (María)\|\|\|/items/13516cb2-250f-4738-961c-d101f67477d7 Torres-Pérez, R. (Rafael)\|\|\|/items/a5a8b84f-5a87-4563-8114-2d402eea8f95 Mancikova, V. (Veronika)\|\|\|/items/286402de-9eee-4e42-b39a-4ff976fe6d36 Ruiz-Llorente, S. (Sergio)\|\|\|/items/94866d6e-caf0-4040-b178-c6702425da61 Martínez-Pérez, J.M. (José Manuel)\|\|\|/items/5227974d-c5c8-45d6-a1de-3985e5732b27 Pita, G. (Guillermo)\|\|\|/items/511d3d5b-17c7-49eb-99a2-b5e30c36b145 Galofre-Ferrater, J.C. (Juan Carlos)\|\|\|/items/e7463ff9-97f4-4119-a307-fd978c0017fd Gonzalez-Neira, A. (Anna)\|\|\|/items/8595341c-963a-4cbe-bdec-8b5267ad1b73 Cascon, A. (Alberto)\|\|\|/items/15e22b8d-8e23-4935-a21e-1796f757fa76 Rodriguez-Antona, C. (Cristina)\|\|\|/items/7e878c35-4151-4360-800d-066cc7de6740 Megías, D. (Diego)\|\|\|/items/d96eda06-62b0-485e-8275-245da5f19ebd Blasco, M.A. (Maria A.)\|\|\|/items/947c369b-148a-4b1e-b1d0-33d7ed216c19 Caleiras, E. (Eduardo)\|\|\|/items/a50fa3bb-6348-4b3b-996d-a6bb73dcdd8c Rodriguez-Perales, S. (Sandra)\|\|\|/items/00d786b0-c4eb-4585-8b7a-30c17f7a74af Robledo, M. (Mercedes)\|\|\|/items/3fa84b0c-f9be-49a8-9290-c1c74231ac11
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv	5p-end FISH TERC TERT promoter methylation TERT promoter mutation Subtelomeric gene expression Telomere shortening
topic	5p-end FISH TERC TERT promoter methylation TERT promoter mutation Subtelomeric gene expression Telomere shortening
description	Background: Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer. Methods and results: In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours. Conclusions: Overall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus.
publishDate	2022
dc.date.none.fl_str_mv	2022 2022-01-01 2022 2022-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10171/122440
url	https://hdl.handle.net/10171/122440
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	John Wiley & Sons
publisher.none.fl_str_mv	John Wiley & Sons
dc.source.none.fl_str_mv	reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra
instname_str	Universidad de Navarra
reponame_str	Dadun. Depósito Académico Digital de la Universidad de Navarra
collection	Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling	Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markersMontero-Conde, C. (Cristina)\|\|\|/items/6d47bc2d-9ef9-4bfd-b374-e423d15b1a25Leandro-García, L.J. (Luis J.)\|\|\|/items/2b44a058-b84c-4a11-ba79-586cd96d0448Martínez-Montes, A.M. (Ángel M.)\|\|\|/items/b516ac80-4289-4500-bf8d-6020481456a1Martínez, P. (Paula)\|\|\|/items/1d9dee42-36b1-44e9-bbe7-6998383a3bf5Moya-Faz, F.J. (Francisco José)\|\|\|/items/6102aa74-fb85-4e24-a56b-0d455483b283Leton, R. (Rocío)\|\|\|/items/292ea14e-4a9d-44f5-b173-d1a1285e3e25Gil, E. (Eduardo)\|\|\|/items/b4f29bae-0e0f-4bd2-a246-99578b4855acMartínez-Puente, N. (Natalia)\|\|\|/items/342fc39d-2ebf-41dd-beb9-a9bd4ebea359Guadalix, S. (Sonsoles)\|\|\|/items/59ca9666-3549-43be-b944-428d56084e83Currás, M. (María)\|\|\|/items/da704e52-e034-47bd-9844-b7ce28b1ef2fGarcia-Tobar, L. (Laura)\|\|\|/items/64b398ed-0d60-4773-9118-e862d5d28ff9Zafón, C. (Carles)\|\|\|/items/25a3e6e5-617d-4937-b3ce-7fed784dbb47Jordá, M. (Mireia)\|\|\|/items/3d80cad9-83d9-4ca7-bce9-327e348710c2Riesco-Eizaguirre, G. (Garcilaso)\|\|\|/items/5b966126-3180-4b86-8215-aa6793d1b0d7García-Montón-González P. (Patricia)\|\|\|/items/066b96d4-7696-4d42-8723-7c86875ee1bfMonteagudo, M. (María)\|\|\|/items/13516cb2-250f-4738-961c-d101f67477d7Torres-Pérez, R. (Rafael)\|\|\|/items/a5a8b84f-5a87-4563-8114-2d402eea8f95Mancikova, V. (Veronika)\|\|\|/items/286402de-9eee-4e42-b39a-4ff976fe6d36Ruiz-Llorente, S. (Sergio)\|\|\|/items/94866d6e-caf0-4040-b178-c6702425da61Martínez-Pérez, J.M. (José Manuel)\|\|\|/items/5227974d-c5c8-45d6-a1de-3985e5732b27Pita, G. (Guillermo)\|\|\|/items/511d3d5b-17c7-49eb-99a2-b5e30c36b145Galofre-Ferrater, J.C. (Juan Carlos)\|\|\|/items/e7463ff9-97f4-4119-a307-fd978c0017fdGonzalez-Neira, A. (Anna)\|\|\|/items/8595341c-963a-4cbe-bdec-8b5267ad1b73Cascon, A. (Alberto)\|\|\|/items/15e22b8d-8e23-4935-a21e-1796f757fa76Rodriguez-Antona, C. (Cristina)\|\|\|/items/7e878c35-4151-4360-800d-066cc7de6740Megías, D. (Diego)\|\|\|/items/d96eda06-62b0-485e-8275-245da5f19ebdBlasco, M.A. (Maria A.)\|\|\|/items/947c369b-148a-4b1e-b1d0-33d7ed216c19Caleiras, E. (Eduardo)\|\|\|/items/a50fa3bb-6348-4b3b-996d-a6bb73dcdd8cRodriguez-Perales, S. (Sandra)\|\|\|/items/00d786b0-c4eb-4585-8b7a-30c17f7a74afRobledo, M. (Mercedes)\|\|\|/items/3fa84b0c-f9be-49a8-9290-c1c74231ac115p-end FISHTERCTERT promoter methylationTERT promoter mutationSubtelomeric gene expressionTelomere shorteningBackground: Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer. Methods and results: In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours. Conclusions: Overall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus.John Wiley & SonsDadun. Depósito Académico Digital Universidad de Navarra20222022-01-0120222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/122440reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1224402026-06-21T12:47:57Z
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Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers

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