Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.

The six major genes involved in hereditary susceptibility for pheochromocytoma (PCC)/paraganglioma (PGL) (RET, VHL, NF1, SDHB, SDHC, and SDHD) have been recently integrated into the same neuronal apoptotic pathway where mutations in any of these genes lead to cell death. In this model, prolyl hydrox...

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Autores: López-Jiménez, Elena, Gómez-López, Gonzalo, Leandro-García, L Javier, Muñoz, Iván, Schiavi, Francesca, Montero-Conde, Cristina, de Cubas, Aguirre A, Ramires, Ricardo, Landa, Iñigo, Leskelä, Susanna, Maliszewska, Agnieszka, Inglada-Pérez, Lucía, de la Vega, Leticia, Rodríguez-Antona, Cristina, Letón, Rocío, Bernal, Carmen, de Campos, José M, Diez-Tascón, Cristina, Fraga, Mario F, Boullosa, Cesar, Pisano, David G, Opocher, Giuseppe, Robledo Batanero, Mercedes, Cascon Soriano, Alberto
Tipo de recurso: artículo
Fecha de publicación:2010
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26013
Acceso en línea:https://hdl.handle.net/20.500.12105/26013
Access Level:acceso abierto
Palabra clave:VON-HIPPEL-LINDAU
RENAL-CELL CARCINOMA
INDUCIBLE FACTOR-I
TUMOR-SUPPRESSOR
EXPRESSION PROFILES
GERMLINE MUTATIONS
MICROARRAY DATA
HYPOXIA
GENE
PARAGANGLIOMA
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/26013
network_acronym_str ES
network_name_str España
repository_id_str
spelling Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.López-Jiménez, ElenaGómez-López, GonzaloLeandro-García, L JavierMuñoz, IvánSchiavi, FrancescaMontero-Conde, Cristinade Cubas, Aguirre ARamires, RicardoLanda, IñigoLeskelä, SusannaMaliszewska, AgnieszkaInglada-Pérez, Lucíade la Vega, LeticiaRodríguez-Antona, CristinaLetón, RocíoBernal, Carmende Campos, José MDiez-Tascón, CristinaFraga, Mario FBoullosa, CesarPisano, David GOpocher, GiuseppeRobledo Batanero, MercedesCascon Soriano, AlbertoVON-HIPPEL-LINDAURENAL-CELL CARCINOMAINDUCIBLE FACTOR-ITUMOR-SUPPRESSOREXPRESSION PROFILESGERMLINE MUTATIONSMICROARRAY DATAHYPOXIAGENEPARAGANGLIOMAThe six major genes involved in hereditary susceptibility for pheochromocytoma (PCC)/paraganglioma (PGL) (RET, VHL, NF1, SDHB, SDHC, and SDHD) have been recently integrated into the same neuronal apoptotic pathway where mutations in any of these genes lead to cell death. In this model, prolyl hydroxylase 3 (EglN3) abrogation plays a pivotal role, but the molecular mechanisms underlying its inactivation are currently unknown. The aim of the study was to decipher specific alterations associated with the different genetic classes of PCCs/PGLs. With this purpose, 84 genetically characterized tumors were analyzed by means of transcriptional profiling. The analysis revealed a hypoxia-inducible factor (HIF)-related signature common to succinate dehydrogenase (SDH) and von Hippel-Lindau (VHL) tumors, that differentiated them from RET and neurofibromatosis type 1 cases. Both canonical HIF-1α and HIF-2α target genes were overexpressed in the SDH/VHL cluster, suggesting that a global HIF deregulation accounts for this common profile. Nevertheless, when we compared VHL tumors with SDHB cases, which often exhibit a malignant behavior, we found that HIF-1α target genes showed a predominant activation in the VHL PCCs. Expression data from 67 HIF target genes was sufficient to cluster SDHB and VHL tumors into two different groups, demonstrating different pseudo-hypoxic signatures. In addition, VHL-mutated tumors showed an unexpected overexpression of EglN3 mRNA that did not lead to significantly different EglN3 protein levels. These findings pave the way for more specific therapeutic approaches for malignant PCCs/PGLs management based on the patient's genetic alteration.OXFORD UNIV PRESSInstituto de Salud Carlos IIIMinisterio de Ciencia e InnovaciónCentro de Investigación Biomédica de Enfermedades Raras20252025-01-1420102010-12-0120102010-12-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12105/26013reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/260132026-06-12T12:43:37Z
dc.title.none.fl_str_mv Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.
title Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.
spellingShingle Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.
López-Jiménez, Elena
VON-HIPPEL-LINDAU
RENAL-CELL CARCINOMA
INDUCIBLE FACTOR-I
TUMOR-SUPPRESSOR
EXPRESSION PROFILES
GERMLINE MUTATIONS
MICROARRAY DATA
HYPOXIA
GENE
PARAGANGLIOMA
title_short Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.
title_full Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.
title_fullStr Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.
title_full_unstemmed Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.
title_sort Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.
dc.creator.none.fl_str_mv López-Jiménez, Elena
Gómez-López, Gonzalo
Leandro-García, L Javier
Muñoz, Iván
Schiavi, Francesca
Montero-Conde, Cristina
de Cubas, Aguirre A
Ramires, Ricardo
Landa, Iñigo
Leskelä, Susanna
Maliszewska, Agnieszka
Inglada-Pérez, Lucía
de la Vega, Leticia
Rodríguez-Antona, Cristina
Letón, Rocío
Bernal, Carmen
de Campos, José M
Diez-Tascón, Cristina
Fraga, Mario F
Boullosa, Cesar
Pisano, David G
Opocher, Giuseppe
Robledo Batanero, Mercedes
Cascon Soriano, Alberto
author López-Jiménez, Elena
author_facet López-Jiménez, Elena
Gómez-López, Gonzalo
Leandro-García, L Javier
Muñoz, Iván
Schiavi, Francesca
Montero-Conde, Cristina
de Cubas, Aguirre A
Ramires, Ricardo
Landa, Iñigo
Leskelä, Susanna
Maliszewska, Agnieszka
Inglada-Pérez, Lucía
de la Vega, Leticia
Rodríguez-Antona, Cristina
Letón, Rocío
Bernal, Carmen
de Campos, José M
Diez-Tascón, Cristina
Fraga, Mario F
Boullosa, Cesar
Pisano, David G
Opocher, Giuseppe
Robledo Batanero, Mercedes
Cascon Soriano, Alberto
author_role author
author2 Gómez-López, Gonzalo
Leandro-García, L Javier
Muñoz, Iván
Schiavi, Francesca
Montero-Conde, Cristina
de Cubas, Aguirre A
Ramires, Ricardo
Landa, Iñigo
Leskelä, Susanna
Maliszewska, Agnieszka
Inglada-Pérez, Lucía
de la Vega, Leticia
Rodríguez-Antona, Cristina
Letón, Rocío
Bernal, Carmen
de Campos, José M
Diez-Tascón, Cristina
Fraga, Mario F
Boullosa, Cesar
Pisano, David G
Opocher, Giuseppe
Robledo Batanero, Mercedes
Cascon Soriano, Alberto
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
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación
Centro de Investigación Biomédica de Enfermedades Raras
dc.subject.none.fl_str_mv VON-HIPPEL-LINDAU
RENAL-CELL CARCINOMA
INDUCIBLE FACTOR-I
TUMOR-SUPPRESSOR
EXPRESSION PROFILES
GERMLINE MUTATIONS
MICROARRAY DATA
HYPOXIA
GENE
PARAGANGLIOMA
topic VON-HIPPEL-LINDAU
RENAL-CELL CARCINOMA
INDUCIBLE FACTOR-I
TUMOR-SUPPRESSOR
EXPRESSION PROFILES
GERMLINE MUTATIONS
MICROARRAY DATA
HYPOXIA
GENE
PARAGANGLIOMA
description The six major genes involved in hereditary susceptibility for pheochromocytoma (PCC)/paraganglioma (PGL) (RET, VHL, NF1, SDHB, SDHC, and SDHD) have been recently integrated into the same neuronal apoptotic pathway where mutations in any of these genes lead to cell death. In this model, prolyl hydroxylase 3 (EglN3) abrogation plays a pivotal role, but the molecular mechanisms underlying its inactivation are currently unknown. The aim of the study was to decipher specific alterations associated with the different genetic classes of PCCs/PGLs. With this purpose, 84 genetically characterized tumors were analyzed by means of transcriptional profiling. The analysis revealed a hypoxia-inducible factor (HIF)-related signature common to succinate dehydrogenase (SDH) and von Hippel-Lindau (VHL) tumors, that differentiated them from RET and neurofibromatosis type 1 cases. Both canonical HIF-1α and HIF-2α target genes were overexpressed in the SDH/VHL cluster, suggesting that a global HIF deregulation accounts for this common profile. Nevertheless, when we compared VHL tumors with SDHB cases, which often exhibit a malignant behavior, we found that HIF-1α target genes showed a predominant activation in the VHL PCCs. Expression data from 67 HIF target genes was sufficient to cluster SDHB and VHL tumors into two different groups, demonstrating different pseudo-hypoxic signatures. In addition, VHL-mutated tumors showed an unexpected overexpression of EglN3 mRNA that did not lead to significantly different EglN3 protein levels. These findings pave the way for more specific therapeutic approaches for malignant PCCs/PGLs management based on the patient's genetic alteration.
publishDate 2010
dc.date.none.fl_str_mv 2010
2010-12-01
2010
2010-12-01
2025
2025-01-14
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/26013
url https://hdl.handle.net/20.500.12105/26013
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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv OXFORD UNIV PRESS
publisher.none.fl_str_mv OXFORD UNIV PRESS
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419319467704320
score 15,812429

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