Abstract
Background. Between 2011 and 2016, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation testing at University of California Los Angeles (UCLA) was performed through LabCorp, using a threshold of 2 to distinguish MGMT methylated from unmethylated tumors. In this study, we sought to determine whether the magnitude of the methylation score correlated with outcome. Methods. We identified 165 newly diagnosed glioblastoma (GBM) isocitrate dehydrogenase (IDH) wild-type and temozolomide-treated upfront patients at UCLA and Kaiser Permanente Los Angeles with LabCorp-derived quantitative MGMT scores obtained on pretreatment tissue samples. Using LabCorp's threshold, we found 102 unmethylated and 63 methylated patients. We then further substratified each group based on the magnitude of the score, and performed Kaplan-Meier and Cox regression analyses of overall survival (OS) and progression-free survival (PFS). Results. We validated that the standard LabCorp threshold of 2 could separate our cohort by survival, showing longer OS and PFS for MGMT methylated patients vs unmethylated patients. Cox regression analysis confirmed that MGMT (<1) patients had worse outcome, with OS and PFS hazard ratios of 2.375 (P = .053) and 2.463 (P = .023), respectively, when compared to the MGMT (1-1.99) patients. Contrary to our expectation, when we substratified the ≥2 (methylated) group, we did not find a dose-dependent relationship between the magnitude of MGMT methylation and improved survival. Conclusions. The MGMT unmethylated group contains a partially methylated group (greater than 1) that shares survival benefits similar to the methylated group. However, we did not demonstrate an association of very high methylation scores with increased survival.These findings will require validation in additional independent clinical data sets.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 194-202 |
| Number of pages | 9 |
| Journal | Neuro-Oncology Practice |
| Volume | 6 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jun 1 2019 |
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Keywords
- Glioblastoma
- Glioma
- MGMT
- Promoter methylation
- Temozolomide
ASJC Scopus subject areas
- Medicine (miscellaneous)
Cite this
Correlation of commercially available quantitative MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation scores and GBM patient survival. / Dovek, Laura; Nguyen, Nhung T.; Ozer, Byram; Li, Ning; Elashoff, Robert M.; Green, Richard M.; Liau, Linda; Leia Nghiemphu, P.; Cloughesy, Timothy F.; Lai, Albert.
In: Neuro-Oncology Practice, Vol. 6, No. 3, 01.06.2019, p. 194-202.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Correlation of commercially available quantitative MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation scores and GBM patient survival
AU - Dovek, Laura
AU - Nguyen, Nhung T.
AU - Ozer, Byram
AU - Li, Ning
AU - Elashoff, Robert M.
AU - Green, Richard M.
AU - Liau, Linda
AU - Leia Nghiemphu, P.
AU - Cloughesy, Timothy F.
AU - Lai, Albert
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Background. Between 2011 and 2016, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation testing at University of California Los Angeles (UCLA) was performed through LabCorp, using a threshold of 2 to distinguish MGMT methylated from unmethylated tumors. In this study, we sought to determine whether the magnitude of the methylation score correlated with outcome. Methods. We identified 165 newly diagnosed glioblastoma (GBM) isocitrate dehydrogenase (IDH) wild-type and temozolomide-treated upfront patients at UCLA and Kaiser Permanente Los Angeles with LabCorp-derived quantitative MGMT scores obtained on pretreatment tissue samples. Using LabCorp's threshold, we found 102 unmethylated and 63 methylated patients. We then further substratified each group based on the magnitude of the score, and performed Kaplan-Meier and Cox regression analyses of overall survival (OS) and progression-free survival (PFS). Results. We validated that the standard LabCorp threshold of 2 could separate our cohort by survival, showing longer OS and PFS for MGMT methylated patients vs unmethylated patients. Cox regression analysis confirmed that MGMT (<1) patients had worse outcome, with OS and PFS hazard ratios of 2.375 (P = .053) and 2.463 (P = .023), respectively, when compared to the MGMT (1-1.99) patients. Contrary to our expectation, when we substratified the ≥2 (methylated) group, we did not find a dose-dependent relationship between the magnitude of MGMT methylation and improved survival. Conclusions. The MGMT unmethylated group contains a partially methylated group (greater than 1) that shares survival benefits similar to the methylated group. However, we did not demonstrate an association of very high methylation scores with increased survival.These findings will require validation in additional independent clinical data sets.
AB - Background. Between 2011 and 2016, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation testing at University of California Los Angeles (UCLA) was performed through LabCorp, using a threshold of 2 to distinguish MGMT methylated from unmethylated tumors. In this study, we sought to determine whether the magnitude of the methylation score correlated with outcome. Methods. We identified 165 newly diagnosed glioblastoma (GBM) isocitrate dehydrogenase (IDH) wild-type and temozolomide-treated upfront patients at UCLA and Kaiser Permanente Los Angeles with LabCorp-derived quantitative MGMT scores obtained on pretreatment tissue samples. Using LabCorp's threshold, we found 102 unmethylated and 63 methylated patients. We then further substratified each group based on the magnitude of the score, and performed Kaplan-Meier and Cox regression analyses of overall survival (OS) and progression-free survival (PFS). Results. We validated that the standard LabCorp threshold of 2 could separate our cohort by survival, showing longer OS and PFS for MGMT methylated patients vs unmethylated patients. Cox regression analysis confirmed that MGMT (<1) patients had worse outcome, with OS and PFS hazard ratios of 2.375 (P = .053) and 2.463 (P = .023), respectively, when compared to the MGMT (1-1.99) patients. Contrary to our expectation, when we substratified the ≥2 (methylated) group, we did not find a dose-dependent relationship between the magnitude of MGMT methylation and improved survival. Conclusions. The MGMT unmethylated group contains a partially methylated group (greater than 1) that shares survival benefits similar to the methylated group. However, we did not demonstrate an association of very high methylation scores with increased survival.These findings will require validation in additional independent clinical data sets.
KW - Glioblastoma
KW - Glioma
KW - MGMT
KW - Promoter methylation
KW - Temozolomide
UR - http://www.scopus.com/inward/record.url?scp=85067649183&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067649183&partnerID=8YFLogxK
U2 - 10.1093/nop/npy028
DO - 10.1093/nop/npy028
M3 - Review article
C2 - 31386024
AN - SCOPUS:85067649183
VL - 6
SP - 194
EP - 202
JO - Neuro-Oncology Practice
JF - Neuro-Oncology Practice
SN - 2054-2577
IS - 3
ER -