Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma

Autores
Panero, Julieta; Alves Paiva, Raquel; Roisman, Alejandro; Santana Lemos, Barbara; Falcao, Roberto P.; Oliveira, Gustavo; Martins, Diego; Stanganelli, Carmen Graciela; Slavutsky, Irma Rosa; Calado, Rodrigo
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm with poor prognosis. Acquired telomerasereverse transcriptase gene promoter (TERTp) mutations are among the most frequent somatic non-codingmutations in cancers. In this study, the prevalence of TERTp mutations in 24 MCL and 21 other lymphoidneoplasias (oLN) was investigated. Eight MCL samples (33%) carried TERTp mutations, two homozygous andsix heterozygous (seven C228T and one C250T), which directly correlated with higher TERT transcription,mitochondrial DNA copy number, and IGHV mutational status in MCL neoplastic cells. TERTp mutations werenot found in oLN. TERTp mutations correlated with more lymphoma proliferation and tumor burden, assuggested by the higher number of lymphoma cells circulating in peripheral blood, and tended to associatewith longer MCL telomeres, especially in homozygous mutants, although not statistically significant.Telomere-biology genes were overexpressed in MCL cells in comparison to healthy lymphocytes, but werenot influenced by mutation status. The findings described for the first time that acquired TERTp mutationsare common in MCL but not in other lymphoid neoplasms. It was also demonstrated that TERTp mutationsassociated with higher TERT mRNA expression in MCL cells in vivo and higher tumor burden, suggestingthese mutations as a driver event in MCL development and progression.
Fil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Alves Paiva, Raquel. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Fil: Roisman, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Santana Lemos, Barbara. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Fil: Falcao, Roberto P.. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Fil: Oliveira, Gustavo. Universidade de Sao Paulo; Brasil
Fil: Martins, Diego. Universidade de Sao Paulo; Brasil
Fil: Stanganelli, Carmen Graciela. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Slavutsky, Irma Rosa. Imex, Conicet-academia Nacional de Medicina; Argentina
Fil: Calado, Rodrigo. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil. Universidade de Sao Paulo; Brasil
Materia
Htert
Mantle Cell Lymphoma
Shelterin
Dna
Leukemia
Limphoma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/45317
Acceder
id CONICETDig_b81b47e6577605503664df8c72c49248
oai_identifier_str oai:ri.conicet.gov.ar:11336/45317
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Acquired TERT promoter mutations activate TERT expression in mantle cell lymphomaPanero, JulietaAlves Paiva, RaquelRoisman, AlejandroSantana Lemos, BarbaraFalcao, Roberto P.Oliveira, GustavoMartins, DiegoStanganelli, Carmen GracielaSlavutsky, Irma RosaCalado, RodrigoHtertMantle Cell LymphomaShelterinDnaLeukemiaLimphomahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm with poor prognosis. Acquired telomerasereverse transcriptase gene promoter (TERTp) mutations are among the most frequent somatic non-codingmutations in cancers. In this study, the prevalence of TERTp mutations in 24 MCL and 21 other lymphoidneoplasias (oLN) was investigated. Eight MCL samples (33%) carried TERTp mutations, two homozygous andsix heterozygous (seven C228T and one C250T), which directly correlated with higher TERT transcription,mitochondrial DNA copy number, and IGHV mutational status in MCL neoplastic cells. TERTp mutations werenot found in oLN. TERTp mutations correlated with more lymphoma proliferation and tumor burden, assuggested by the higher number of lymphoma cells circulating in peripheral blood, and tended to associatewith longer MCL telomeres, especially in homozygous mutants, although not statistically significant.Telomere-biology genes were overexpressed in MCL cells in comparison to healthy lymphocytes, but werenot influenced by mutation status. The findings described for the first time that acquired TERTp mutationsare common in MCL but not in other lymphoid neoplasms. It was also demonstrated that TERTp mutationsassociated with higher TERT mRNA expression in MCL cells in vivo and higher tumor burden, suggestingthese mutations as a driver event in MCL development and progression.Fil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Alves Paiva, Raquel. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; BrasilFil: Roisman, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Santana Lemos, Barbara. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; BrasilFil: Falcao, Roberto P.. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; BrasilFil: Oliveira, Gustavo. Universidade de Sao Paulo; BrasilFil: Martins, Diego. Universidade de Sao Paulo; BrasilFil: Stanganelli, Carmen Graciela. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Slavutsky, Irma Rosa. Imex, Conicet-academia Nacional de Medicina; ArgentinaFil: Calado, Rodrigo. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil. Universidade de Sao Paulo; BrasilJohn Willey & Sons2016-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/45317Panero, Julieta; Alves Paiva, Raquel; Roisman, Alejandro; Santana Lemos, Barbara; Falcao, Roberto P.; et al.; Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma; John Willey & Sons; American Journal Of Hematology; 91; 5; 2-2016; 481-4850361-86091096-8652CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.24324info:eu-repo/semantics/altIdentifier/doi/10.1002/ajh.24324info:eu-repo/semantics/altIdentifier/pmid/26852175info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:05Zoai:ri.conicet.gov.ar:11336/45317instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:41:05.964CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma
title Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma
spellingShingle Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma
Panero, Julieta
Htert
Mantle Cell Lymphoma
Shelterin
Dna
Leukemia
Limphoma
title_short Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma
title_full Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma
title_fullStr Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma
title_full_unstemmed Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma
title_sort Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma
dc.creator.none.fl_str_mv Panero, Julieta
Alves Paiva, Raquel
Roisman, Alejandro
Santana Lemos, Barbara
Falcao, Roberto P.
Oliveira, Gustavo
Martins, Diego
Stanganelli, Carmen Graciela
Slavutsky, Irma Rosa
Calado, Rodrigo
author Panero, Julieta
author_facet Panero, Julieta
Alves Paiva, Raquel
Roisman, Alejandro
Santana Lemos, Barbara
Falcao, Roberto P.
Oliveira, Gustavo
Martins, Diego
Stanganelli, Carmen Graciela
Slavutsky, Irma Rosa
Calado, Rodrigo
author_role author
author2 Alves Paiva, Raquel
Roisman, Alejandro
Santana Lemos, Barbara
Falcao, Roberto P.
Oliveira, Gustavo
Martins, Diego
Stanganelli, Carmen Graciela
Slavutsky, Irma Rosa
Calado, Rodrigo
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Htert
Mantle Cell Lymphoma
Shelterin
Dna
Leukemia
Limphoma
topic Htert
Mantle Cell Lymphoma
Shelterin
Dna
Leukemia
Limphoma
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm with poor prognosis. Acquired telomerasereverse transcriptase gene promoter (TERTp) mutations are among the most frequent somatic non-codingmutations in cancers. In this study, the prevalence of TERTp mutations in 24 MCL and 21 other lymphoidneoplasias (oLN) was investigated. Eight MCL samples (33%) carried TERTp mutations, two homozygous andsix heterozygous (seven C228T and one C250T), which directly correlated with higher TERT transcription,mitochondrial DNA copy number, and IGHV mutational status in MCL neoplastic cells. TERTp mutations werenot found in oLN. TERTp mutations correlated with more lymphoma proliferation and tumor burden, assuggested by the higher number of lymphoma cells circulating in peripheral blood, and tended to associatewith longer MCL telomeres, especially in homozygous mutants, although not statistically significant.Telomere-biology genes were overexpressed in MCL cells in comparison to healthy lymphocytes, but werenot influenced by mutation status. The findings described for the first time that acquired TERTp mutationsare common in MCL but not in other lymphoid neoplasms. It was also demonstrated that TERTp mutationsassociated with higher TERT mRNA expression in MCL cells in vivo and higher tumor burden, suggestingthese mutations as a driver event in MCL development and progression.
Fil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Alves Paiva, Raquel. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Fil: Roisman, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Santana Lemos, Barbara. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Fil: Falcao, Roberto P.. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Fil: Oliveira, Gustavo. Universidade de Sao Paulo; Brasil
Fil: Martins, Diego. Universidade de Sao Paulo; Brasil
Fil: Stanganelli, Carmen Graciela. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Slavutsky, Irma Rosa. Imex, Conicet-academia Nacional de Medicina; Argentina
Fil: Calado, Rodrigo. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil. Universidade de Sao Paulo; Brasil
description Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm with poor prognosis. Acquired telomerasereverse transcriptase gene promoter (TERTp) mutations are among the most frequent somatic non-codingmutations in cancers. In this study, the prevalence of TERTp mutations in 24 MCL and 21 other lymphoidneoplasias (oLN) was investigated. Eight MCL samples (33%) carried TERTp mutations, two homozygous andsix heterozygous (seven C228T and one C250T), which directly correlated with higher TERT transcription,mitochondrial DNA copy number, and IGHV mutational status in MCL neoplastic cells. TERTp mutations werenot found in oLN. TERTp mutations correlated with more lymphoma proliferation and tumor burden, assuggested by the higher number of lymphoma cells circulating in peripheral blood, and tended to associatewith longer MCL telomeres, especially in homozygous mutants, although not statistically significant.Telomere-biology genes were overexpressed in MCL cells in comparison to healthy lymphocytes, but werenot influenced by mutation status. The findings described for the first time that acquired TERTp mutationsare common in MCL but not in other lymphoid neoplasms. It was also demonstrated that TERTp mutationsassociated with higher TERT mRNA expression in MCL cells in vivo and higher tumor burden, suggestingthese mutations as a driver event in MCL development and progression.
publishDate 2016
dc.date.none.fl_str_mv 2016-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/45317
Panero, Julieta; Alves Paiva, Raquel; Roisman, Alejandro; Santana Lemos, Barbara; Falcao, Roberto P.; et al.; Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma; John Willey & Sons; American Journal Of Hematology; 91; 5; 2-2016; 481-485
0361-8609
1096-8652
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45317
identifier_str_mv Panero, Julieta; Alves Paiva, Raquel; Roisman, Alejandro; Santana Lemos, Barbara; Falcao, Roberto P.; et al.; Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma; John Willey & Sons; American Journal Of Hematology; 91; 5; 2-2016; 481-485
0361-8609
1096-8652
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.24324
info:eu-repo/semantics/altIdentifier/doi/10.1002/ajh.24324
info:eu-repo/semantics/altIdentifier/pmid/26852175
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Willey & Sons
publisher.none.fl_str_mv John Willey & Sons
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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