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J Neurooncol. 2012 Mar;107(1):147-53. doi: 10.1007/s11060-011-0721-3. Epub 2011 Oct 4.

O⁶-methylguanine-DNA methyltransferase promoter methylation in 45 primary central nervous system lymphomas: quantitative assessment of methylation and response to temozolomide treatment.

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Department of Neuro-Oncology/Neurosurgery, Comprehensive Cancer Center, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama 350-1298, Japan.


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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