Gliomas

Low Grade Glioma

Outlines from Neurosurgery Self-assessment - Q&A

• 1° goal in initial Tx of LGG is max. safe resection → assoc. w/ prolonged survival, sz pPx, ↓ risk of transformation;
• Qx for suspected LGGs challenges:
  • GTR is difficult d/t the diffusely infiltrative growth pattern of LGG → difficult to id the exact tumor borders; ∴ image guidance w/ FLAIR is crucial.
  • Histopathological undergrading is common w/ Bx, as LGG often exhibits focal areas of malignant transformation (anaplastic foci). To avoid this and reduce subsequent treatment failure, the surgical goal is to perform precise tissue sampling from a potential anaplastic focus.
  • "Eloquent" localization → awake Qx ± functional mapping

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