In the revised World Health Organization (WHO) Classification of Tumors of the Central Nervous System, molecular genetic alterations have been incorporated to the classic histology of primary brain tumors (PBT), including isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations and methylation of the O6 -methylguanine-DNA methyltransferase promoter (MGMT). The IDH mutation is associated with a better prognosis in patients with glioma, independently of histological parameters and tumor grade. MGMT methylation silences the MGMT gene and reduces the ability of tumor cells to repair damage caused by temozolomide and other alkylating agents. Moreover, MGMT. Methylation confers a better prognosis to high-grade gliomas.
The Methylation Specific MLPA (MS-MLPA) assay has been used to in to detect IDH type 1/ type 2-point mutations and MGMT methylation. In the MS-MLPA assay the sequence targeted by specific probes contains a restriction site for the HhaI endonuclease, able to recognize the unmethylated GCGC sequence. The comparison of the peak size of the methylation specific probes, between a sample and a control, provide information about the levels of methylation of the specific DNA regions targeted by the probes on formalin-fixed, paraffin-embedded (FFPE) tissue sections.
This study investigated 30 patients of primary brain tumors enrolled between January 2021 to February 2022 at the Aga Khan University Hospital. The male to female ratio was 2:1. Mean age was 38 years and patients’ ages ranged from 19 to 70 years. 14 cases (47%) were positive for Isocitrate dehydrogenase mutation. Among IDH Positive patients, 12 cases exhibit IDH1 (P. R132H/P. R132C) point mutation and 2 cases exhibits IDH2 (R172K) point mutation. 16(53%) of the cases had no mutation detected. Whereas Methylation of MGMT was detectable in 18 out of the 30 patients exanimated (60%).
Practical implementation of routine molecular workup of CNS tumors is compromised by impractically long turnaround times and economic restraints, based on our results, we advocate a stepwise approach, providing fast-track results obtained by MLPA for first-line therapy decisions within a week after surgery.
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