Karschnia, Philipp;
Teske, Nico;
Siller, Sebastian;
Dorostkar, Mario M;
Weller, Jonathan;
Herms, Jochen;
Baehring, Joachim M;
von Baumgarten, Louisa;
Tonn, Joerg-Christian;
Thon, Niklas
PATH-28. EXTENT AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION DEPEND ON IDH MUTATION AND 1p19q CO-DELETION IN GLIOMA WHO GRADE II
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Media type:
E-Article
Title:
PATH-28. EXTENT AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION DEPEND ON IDH MUTATION AND 1p19q CO-DELETION IN GLIOMA WHO GRADE II
Contributor:
Karschnia, Philipp;
Teske, Nico;
Siller, Sebastian;
Dorostkar, Mario M;
Weller, Jonathan;
Herms, Jochen;
Baehring, Joachim M;
von Baumgarten, Louisa;
Tonn, Joerg-Christian;
Thon, Niklas
Description:
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>INTRODUCTION</jats:title>
<jats:p>Methylation of the promotor region of the O6-methylguanin-DNA-methyltransferase (MGMT) gene is associated with increased survival in low- and high-grade glioma. It is unknown whether this association also applies to the 2016 WHO categories of glioma WHO grade II.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>MATERIAL AND METHODS</jats:title>
<jats:p>We retrospectively searched the institutional database of the Center for Neuro-Oncology for patients with glioma WHO grade II. Patients were assigned to one of three groups according to the 2016 WHO classification system: 1. 1p19q co-deleted oligodendroglioma, IDH mutant; 2. 1p19q non-codeleted astrocytoma, IDH mutant; 3. 1p19q non-codeleted astrocytoma, IDH wild-type. MGMT methylation status was analysed using Sanger sequencing of the CpG sites 74-98 within the MGMT promotor region. The total number of methylated CpG sites was calculated for each patient.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESULTS</jats:title>
<jats:p>155 patients with glioma WHO grade II were encountered, including 81 1p19q co-deleted, IDH mutant oligodendrogliomas; 54 IDH mutant astrocytomas; and 20 IDH wild-type astrocytomas. The mean number of methylated CpG sites among oligodendrogliomas was significantly higher when compared to IDH mutant astrocytomas (18.9 ± 0.4 vs. 16.3 ± 0.6; p = 0.001). In turn, the number of methylated CpG sites among IDH mutant astrocytomas was higher when compared to IDH wild-type astrocytomas (16.3 ± 0.6 vs. 12.3 ± 1.9; p = 0.007). Median follow-up was estimated at 35 months. Median time to malignant progression was 87 months for all patients, and median overall survival was not reached. In the entire cohort, a larger number of methylated CpG sites was prognostic of overall survival and time to malignant progression. When analysed separately for the three WHO subgroups, a similar association was only retained in IDH wild-type astrocytoma.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>CONCLUSION</jats:title>
<jats:p>In our series of WHO II gliomas, MGMT promotor methylation appeared strongly associated with 1p19q codeletion and IDH mutations. MGMT promotor methylation was only prognostic in IDH wild-type astrocytoma.</jats:p>
</jats:sec>