Detecting genomic differences in pediatric patients with brain tumors under Temozolomide treatment

• Main Authors: Meng-Shu Chieh, 階孟書
• Other Authors: Yann-Jang Chen
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/68618798651184788162

碩士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 95 === Many studies indicated the expression of O6-methylguanine DNA methyltransferase (MGMT) enzyme was related to the efficacy of temozolomide in patients with tumors. Due to the fact that the methylation of CpG island on MGMT promoter inhibits the expression of MGMT protein, it was confirmed that the methylaiton of MGMT promoter was associated with the outcomes of patients after the temozolomide treatment. However, some studies did not agree with this result. Thus, more evidences are required. In this research, we hypothized there were genomic differences or the common lesions in these patients, which leads to different efficacies of temozolomide. In this study, 21 children with brain tumors under temozolomide treatment were recruited. After 6 cycles of temozolomide, patients whose tumors reduced in size considerably or kept or slowed down in size were classified as temozolomide-responding patients as measured by MRI. Others were assigned as temozolomide-resistant patients. The results from MRI were also compared to those from methylation-specific PCR (MSP) analysis. On the other hand, the genomic differences in those patients were observed using Comparative Gnomic hybridization (CGH) and the relations between results of CGH and the survival time were investigated. Results showed that the methylation rate in temozolomide-responding patients were higher than that in temozolomide-resistant patients. However, there was no relation between MSP results and survival after the temozolomide treatment (p=0.192). In all of brain tumor patients, PA (pilocytic astrocytoma) had +Xq21 (n=2) in common; two-third of AA (anaplstic astrocytoma) had l +7p, +7q21-ter, +9q34, and -22 (n=3) in common; two-third of G (glioblastoma multiforme) had +1q (n=3) in common; two-third of M (medulloblastoma) had +18q in common; AT/RT (atypical teratoid / rhabdoid tumor) had +17q11.2-21 and +17q25 (n=3) in common. However, there was some inconsistency in results from those of recurrences. In temozolomide-responding group, 44.4% (4/9) were +17q11.2-21, +17q25 and +19p. In temozolomide-resistant group, 28.6% (2/7) were +1q, +3q28-29, -6q21-24, +7q21-ter, +8q13-23, -10p13-ter, -11q, +12q13-14, -14q23-24, -14q32 and -22q. The patients who had +8q in the primary tumor from the initial surgery had a shorter overall survival or survival after temozolomide than those who had non-+8q (n=12, p=0.001). In conclusion, the genomic imbalance of +17q11.2-21, +17q25 and +19p were maybe the references to the efficacy of the temozolomide treatment in addition to MGMT hypermethylation. More evidences will be needed to clarify the correlation between the temozolomide treatment and clinical meaning of +8q variations.