Acquired TERT promoter mutations activate TERT expression in mantle cell lymphoma

Authors
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
Publication Year
2016
Language
English
Format
article
Status
Published version
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.
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
Subject
HTERT
MANTLE CELL LYMPHOMA
SHELTERIN
DNA
LEUKEMIA
LIMPHOMA
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Patología
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/45317