Department of Clinical Neurosciences, Foothills Medical Centre, 1403 29th St NW, Calgary, Alberta, Canada.
Neuro Oncol. 2010 Jul;12(7):756-60. doi: 10.1093/neuonc/noq032. Epub 2010 Apr 13.
Molecular alterations in glioblastoma have the potential to guide treatment. Here, we explore the relationship between temozolomide (TMZ) response and O(6)-methylguanine DNA methyltransferase (MGMT) status in brain tumor initiating cells (BTICs). Methylation, expression, and sensitivity were assessed in 20 lines; associations were evaluated by Fisher's exact test. Some BTICs were sensitive. Sensitivity to TMZ was only associated with protein expression (P = .001). There were atypical BTICs including TMZ-resistant lines in which the methylation-specific PCR reaction revealed both methylated and unmethylated bands. BTICs are not uniformly resistant to TMZ; some are sensitive. MGMT status does not predict TMZ response with high precision.
胶质母细胞瘤中的分子改变有可能指导治疗。在这里,我们探讨了替莫唑胺(TMZ)反应与脑肿瘤起始细胞(BTIC)中 O(6)-甲基鸟嘌呤 DNA 甲基转移酶(MGMT)状态之间的关系。在 20 条系中评估了甲基化、表达和敏感性;通过 Fisher 精确检验评估关联。一些 BTICs 对 TMZ 敏感。对 TMZ 的敏感性仅与蛋白表达相关(P =.001)。存在非典型 BTICs,包括 TMZ 耐药系,其中甲基化特异性 PCR 反应显示出甲基化和非甲基化条带。BTICs 对 TMZ 并非普遍耐药;有些 BTICs 对 TMZ 敏感。MGMT 状态并不能高精度预测 TMZ 反应。