Abstract:
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.
Author affiliation: 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
Author affiliation: Alves Paiva, Raquel. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Author affiliation: 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
Author affiliation: Santana Lemos, Barbara. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Author affiliation: Falcao, Roberto P.. Universidade de Sao Paulo; Brasil. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil
Author affiliation: Oliveira, Gustavo. Universidade de Sao Paulo; Brasil
Author affiliation: Martins, Diego. Universidade de Sao Paulo; Brasil
Author affiliation: Stanganelli, Carmen Graciela. Academia Nacional de Medicina de Buenos Aires; Argentina
Author affiliation: Slavutsky, Irma Rosa. Imex, Conicet-academia Nacional de Medicina; Argentina
Author affiliation: Calado, Rodrigo. Fundação de Amparo À Pesquisa do Estado de São Paulo; Brasil. Universidade de Sao Paulo; Brasil