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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.
- Authors
Adachi, Jun-Ichi; Mishima, Kazuhiko; Wakiya, Kenji; Suzuki, Tomonari; Fukuoka, Kohei; Yanagisawa, Takaaki; Matsutani, Masao; Sasaki, Atsushi; Nishikawa, Ryo
- 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.
- Publication
Journal of neuro-oncology, 2012, Vol 107, Issue 1, p147
- ISSN
1573-7373
- Publication type
Journal Article
- DOI
10.1007/s11060-011-0721-3