आणविक और आनुवंशिक चिकित्सा

Co-deletion of 1p/19q is Strongly Correlated with a High Level of MGMT Promoter Methylation in High Grade Gliomas as Revealed by Pyrosequencing

Abstract

Ross C. Laxton, Lawrence Doey, Miren Aizpurua, Istvan Bodi, Andrew King, Chris Chandler, Ranj Bhangoo, Ron Beaney, Lucy Brazil, Keyoumars Ashkan and Safa Al-Sarraj

Background: MGMT methylation, along with 1p/19q co-deletion and IDH1 mutation, is an important biomarker in high grade gliomas. MGMT methylation indicates an improved response to temozolomide chemotherapy; patients with 1p/19q co-deleted anaplastic oligodendrogliomas benefit preferentially from adjuvant chemotherapy. Pyrosequencing is a method that allows the level of MGMT methylation to be measured in a quantitative manner.
Aim: To compare the mean MGMT promoter methylation level of high grade gliomas and correlate it with other clinical parameters and markers including 1p/19q co-deletion and mutation to IDH1or IDH2.
Methods: Pyrosequencing was used to quantitatively detect the level of MGMT promoter methylation for 171 high grade gliomas mutations to IDH1 and IDH2 genes were also detected by pyrosequencing, or immunohistochemistry (n=166). Screening for 1p/19q deletion was by fluorescence in situ hybridisation (n=46). Statistical analysis was performed using R-Stats v2.15.2.
Results: Higher methylation was correlated with lower grade and mutation to either IDH1 or IDH2 (27.0% vs. 16.6% p = 0.008; and 27.5 vs. 16.1 p = 0.002 respectively). 1p/19q co-deletion versus non co-deletion was associated with a particularly high level of methylation (42.2% vs. 17.7% p = 0.001). No significant differences were seen for age or gender.
Conclusions: The results offer a potential explanation for the improved prognosis seen in glioma patients with 1p/19q co-deletion.