Gliomas: Difference between revisions
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*MGMT promoter methylation in GBM is a prognostic and predictive biomarker indicating response to chemoradiation. | *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. | *Patients with MGMT promoter methylated tumors benefit most from treatment with TMZ. | ||
*Absence of MGMT promoter methylation | *<u>Absence of MGMT promoter methylation</u> → ↓ benefit from chemoradiation. | ||
*MGMT promoter methylation is a useful predictive biomarker for stratifying elderly GBM patients for RT versus alkylating agent chemotherapy. | *MGMT promoter methylation is a useful predictive biomarker for stratifying elderly GBM patients for RT versus alkylating agent chemotherapy. | ||
===Telomerase Reverse Transcriptase (TERT)=== | ===Telomerase Reverse Transcriptase (TERT)=== | ||
*Telomeres, at the ends of chromosomes, shorten | *Telomeres, at the ends of chromosomes, shorten w/ each cell division - <u>limit to cell replication</u>. | ||
*Telomerase, an enzyme that helps to maintain the length of telomeres; | *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. | *Gliomas can bypass this limit via overexpression of TERT due to mutations in the promoter. | ||
| Line 18: | Line 18: | ||
*IDH 1 & 2 glu metabolism enzymes | *IDH 1 & 2 glu metabolism enzymes | ||
*Mutations in IDH1/2 → abnml form of IDH enzyme → ↑ 2-hydroxyglutarate (2-HG) | *Mutations in IDH1/2 → abnml form of IDH enzyme → ↑ 2-hydroxyglutarate (2-HG) | ||
**2-HG is a toxic metabolite | **2-HG is a toxic metabolite → promote tumor growth. | ||
*IDH mutations assoc. w/ better prognosis (LGG) | *IDH mutations assoc. w/ better prognosis (LGG) | ||
*IDH wild type (no mutations of the IDH) - worse prognosis because assoc. w/ HGG | *IDH wild type (no mutations of the IDH) - worse prognosis because assoc. w/ HGG | ||
[[Category:Neuro-Oncology]] | [[Category:Neuro-Oncology]] | ||
Revision as of 02:16, 19 August 2023
- Low Grade Glioma
- High Grade Glioma
Molecular markers in Gliomas
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.
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
Isocitrate dehydrogenase (IDH) 1/2
- 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