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  • Title: O⁶-methylguanine-DNA methyltransferase promoter methylation in 45 primary central nervous system lymphomas: quantitative assessment of methylation and response to temozolomide treatment.
    Author: Adachi J, Mishima K, Wakiya K, Suzuki T, Fukuoka K, Yanagisawa T, Matsutani M, Sasaki A, Nishikawa R.
    Journal: J Neurooncol; 2012 Mar; 107(1):147-53. PubMed ID: 21968944.
    Abstract:
    Favorable responses to temozolomide chemotherapy have recently been reported in primary central nervous system lymphoma (PCNSL) patients who are refractory to high-dose methotrexate therapy. The gene encoding the DNA repair enzyme O (6)-methylguanine-DNA methyltransferase (MGMT) is transcriptionally silenced by promoter methylation in several human tumors, including gliomas and systemic lymphomas. MGMT promoter methylation is also a prognostic marker in glioblastoma patients treated with temozolomide. To validate temozolomide treatment in PCNSL, we applied methylation-sensitive high resolution melting (MS-HRM) analysis to quantitate MGMT methylation in PCNSL. MGMT promoter methylation was detected in tumors from 23 (51%) of 45 PCNSL patients, 11 of which were considered to have high (more than 70.0%) methylation status. Of the five recurrent PCNSLs treated with temozolomide, four cases responded, with three achieving complete response and one, a partial response. All four responsive PCNSLs had methylated MGMT promoters, whereas the non-responsive recurrent PCNSL did not. Thus, the use of quantitative MS-HRM analysis for the detection of MGMT promoter methylation has been suggested in PCNSL for the first time. The assay allows rapid and high-throughput evaluation of the MGMT methylation status, and seems to be promising in clinical settings. MGMT promoter methylation may become a useful marker for predicting the response of PCNSLs to temozolomide.
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