O(6)-Methylguanine-DNA Methyltransferase (MGMT)

The O(6)-Methylguanine-DNA Methyltransferase (MGMT) is a DNA repair enzyme that counteracts the chemotherapeutic effects of alkylating agents.
Cancer-related methylation of the MGMT promoter region results in less DNA repair activity, including that induced by temozolomide (TMZ).
MGMT promoter methylation in GBM is a prognostic and predictive biomarker indicating response to chemoradiation.
Patients with MGMT promoter methylated tumors benefit most from treatment with TMZ.
Absence of MGMT promoter methylation → ↓ benefit from chemoradiation.
MGMT promoter methylation is a useful predictive biomarker for stratifying elderly GBM patients for RT versus alkylating agent chemotherapy.

MGMT אנזים רפרטיבי של DNA פגוע.
אם האנזים פעיל, הוא מתקן DNA שנפגע כתוצאה מכימו.
אם יש מטילציה בפרומוטור של האנזים, אז האנזים לא מסונטז ואז יש תגובה טובה לכימו.
אם אין מטילציה של הפרומוטור, אז האנזים מסונטז ומה שעושה הכימו, הוא מתקן = תגובה לא טובה לכימו.

Telomerase Reverse Transcriptase (TERT)

Telomeres, at the ends of chromosomes, shorten w/ each cell division - limit to cell replication.
Telomerase, an enzyme that helps to maintain the length of telomeres;
Gliomas can bypass this limit via overexpression of TERT due to mutations in the promoter.
overactive TERT → maintaining telomere length → facilitating tumor expression

IDH 1 & 2 glu metabolism enzymes
Mutations in IDH1/2 → abnml form of IDH enzyme → ↑ 2-hydroxyglutarate (2-HG)
- 2-HG is a toxic metabolite → promote tumor growth.
IDH mutations assoc. w/ better prognosis (LGG)
IDH wild type (no mutations of the IDH) - worse prognosis because assoc. w/ HGG