The Changes in MGMT Promoter Methylation Status in Initial and Recurrent Glioblastomas.
To evaluate the mechanism of the development of therapeutic resistance after temozolomide treatment, we focused on changes in O(6)-methylguanine DNA methyltransferase (MGMT) and mismatch repair (MMR) between initial and recurrent glioblastomas. Tissue samples obtained from 24 paired histologically confirmed initial and recurrent adult glioblastoma patients who were initially treated with temozolomide were used for MGMT and MMR gene promoter methylation status and protein expression analysis using methylation-specific multiplex ligation probe amplification (MS-MLPA), methylation-specific polymerase chain reaction (MSP), and immunohistochemical staining. 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 initial and recurrent tumors. 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.
Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea.
Chul-Kee
CK
Park
Ja Eun
JE
Kim
Ji Young
JY
Kim
Sang Woo
SW
Song
Jin Wook
JW
Kim
Seung Hong
SH
Choi
Tae Min
TM
Kim
Se-Hoon
SH
Lee
Il Han
IH
Kim
Sung-Hye
SH
Park