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845 DNA Promoter Methylation and Protein Quantitative Analysis of P16INK4a and Bim in Childhood B Non-Hodgkin Lymphomas

2012; Elsevier BV; Volume: 48; Linguagem: Inglês

10.1016/s0959-8049(12)71478-8

1879-0852

M.C.S. Robaina, Viviane Oliveira Arruda, Lídia Maria Magalhães de Rezende, Gisele M. Vasconcelos, Roberta Soares Faccion, I.E.P. Arcuri, Alexandre Gustavo Apa, J.A. Dobbbin, Claudete Esteves Klumb,

Lymphoma Diagnosis and Treatment

Background: To evaluate the mechanism of the development of therapeutic resistance after temozolomide treatment, we focused on changes in O 6methylguanine DNA methyltransferase (MGMT) and mismatch repair (MMR) between primary and recurrent glioblastomas.Material and Methods: Tissue samples obtained from 24 paired histologically confirmed primary and recurrent adult glioblastoma patients who were initially treated with temozolomide were utilised for MGMT and MMR gene promoter methylation status and protein expression analysis using methylationspecific multiplex ligation probe amplification (MS-MLPA), methylation-specific polymerase chain reaction (MSP) and immunohistochemical (IHC) staining.Results: There was a significant decrease in the methylation ratio of the MGMT promoter determined by MS-MLPA, which was not detectable with MSP, and MGMT protein expression changes were not remarkable.However, there was no epigenetic variability in MMR genes, and a relatively homogeneous expression of MMR proteins was observed in primary and recurrent tumors.Conclusions: We conclude that the development of reduced methylation in the MGMT promoter is one of the mechanisms for acquiring therapeutic resistance after temozolomide treatment in glioblastomas.