Gliomas: Difference between revisions

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* Low Grade Glioma
{{NoteBox|secondary}}<strong>Related pages</strong>
* High Grade Glioma
* [[Molecular markers in Gliomas]]
{{NoteBoxEnd}}


==Molecular markers in Gliomas ==
= WHO 2016 Classification of Infiltrating Gliomas =
=== O(6)-Methylguanine-DNA Methyltransferase (MGMT) ===
<table class="wikitable">
*The O(6)-Methylguanine-DNA Methyltransferase (MGMT) is a DNA repair enzyme that counteracts the chemotherapeutic effects of alkylating agents.
    <tr>
*Cancer-related methylation of the MGMT promoter region results in less DNA repair activity, including that induced by temozolomide (TMZ).
      <th>Diagnosis</th>
*MGMT promoter methylation in GBM is a prognostic and predictive biomarker indicating response to chemoradiation.
      <th>Common Mutations</th>
*Patients with MGMT promoter methylated tumors benefit most from treatment with TMZ.
      <th>Additional Characteristics</th>
*Absence of MGMT promoter methylation results in a smaller survival benefit from chemoradiation.
    </tr>
*MGMT promoter methylation is a useful predictive biomarker for stratifying elderly GBM patients for RT versus alkylating agent chemotherapy.
 
===Telomerase Reverse Transcriptase (TERT)===
    <tr>
*Telomeres, at the ends of chromosomes, shorten with each cell division, providing a limit to cell replication.
      <td colspan="3"><strong>[[Astrocytoma]]</strong></td>
*Telomerase, an enzyme that helps to maintain the length of telomeres;
    </tr>
*Gliomas can bypass this limit via overexpression of TERT due to mutations in the promoter.
    <tr>
*overactive TERT → maintaining telomere length → facilitating tumor expression
      <td>[[Diffuse astrocytoma]], IDH-mutant (WHO grade II)</td>
===Isocitrate dehydrogenase (IDH) 1/2===
      <td rowspan="7">
*IDH 1 & 2 glu metabolism enzymes
* IDH1/IDH2
*Mutations in IDH1/2 → abnml form of IDH enzyme → ↑ 2-hydroxyglutarate (2-HG)  
* ATRX
**2-HG is a toxic metabolite →promote tumor growth.
* TP53
*IDH mutations assoc. w/ better prognosis (LGG)
* TERT promoter
*IDH wild type (no mutations of the IDH) - worse prognosis because assoc. w/ HGG
* EGFR amplification
* +7/−10
* PTEN mutation/loss
* H3.3 p.K27M</td>
      <td>Usually younger patients (40–50 years old); present as lower gliomas; most glioblastomas in this group are secondary</td>
    </tr>
    <tr>
      <td>Anaplastic astrocytoma, IDH-mutant (WHO grade III)</td>
      <td></td>
    </tr>
    <tr>
      <td>[[Glioblastoma]], IDH-mutant (WHO grade IV)</td>
      <td></td>
    </tr>
    <tr>
      <td>Diffuse astrocytoma, IDH-wildtype (WHO grade II)</td>
      <td>Usually older patients (>55 years old); present as high-grade gliomas; most glioblastomas in this group are primary</td>
    </tr>
    <tr>
      <td>Anaplastic astrocytoma, IDH-wildtype (WHO grade III)</td>
      <td></td>
    </tr>
    <tr>
      <td>Glioblastoma, IDH-wildtype (WHO grade IV)</td>
      <td></td>
    </tr>
    <tr>
      <td>Diffuse midline glioma, H3 -K27M-mutant</td><td>Midline location, infiltrating on histology, H3.3 p.K27M mutation</td></tr>
    <tr>
      <td colspan="3"><strong>[[Oligodendroglioma]]</strong></td>
    </tr>
    <tr>
      <td>Oligodendroglioma, IDH-mutant, 1p/19q codeleted (WHO grade II)</td>
      <td>IDH1/IDH2<br>1p/19q codeletion</td>
      <td>ATRX is wild-type (ATRX mutations are mutually exclusive with 1p/19q codeletion), strong correlation with perinuclear clearing histology</td>
    </tr>
    <tr>
      <td>Anaplastic oligodendroglioma, IDH-mutant, 1p/19q codeleted (WHO grade III)</td>
      <td></td>
      <td></td>
    </tr>
 
</table>
 
=Low Grade Glioma=
<div class="mw-message-box-info mw-message-box">
==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
</div>
 
= High Grade Glioma =
<hr>
 
= Prognostic Factors =
{{NoteBox|secondary}}The data from the pre-IDH era indicated a <u>poorer prognosis</u> associated w/ the following factors:
* >40 y/o (most sig. unfavorable factor)
* Hx of astrocytoma
* SOL ≥6 cm
* Crossing the midline
* Preexisting deficit preQx {{NoteBoxEnd}}


[[Category:Neuro-Oncology]]
[[Category:Neuro-Oncology]]

Latest revision as of 04:07, 5 March 2024

Related pages

WHO 2016 Classification of Infiltrating Gliomas

Diagnosis Common Mutations Additional Characteristics
Astrocytoma
Diffuse astrocytoma, IDH-mutant (WHO grade II)
  • IDH1/IDH2
  • ATRX
  • TP53
  • TERT promoter
  • EGFR amplification
  • +7/−10
  • PTEN mutation/loss
  • H3.3 p.K27M
 Usually younger patients (40–50 years old); present as lower gliomas; most glioblastomas in this group are secondary
Anaplastic astrocytoma, IDH-mutant (WHO grade III)
Glioblastoma, IDH-mutant (WHO grade IV)
Diffuse astrocytoma, IDH-wildtype (WHO grade II) Usually older patients (>55 years old); present as high-grade gliomas; most glioblastomas in this group are primary
Anaplastic astrocytoma, IDH-wildtype (WHO grade III)
Glioblastoma, IDH-wildtype (WHO grade IV)
Diffuse midline glioma, H3 -K27M-mutantMidline location, infiltrating on histology, H3.3 p.K27M mutation
Oligodendroglioma
Oligodendroglioma, IDH-mutant, 1p/19q codeleted (WHO grade II) IDH1/IDH2
1p/19q codeletion		 ATRX is wild-type (ATRX mutations are mutually exclusive with 1p/19q codeletion), strong correlation with perinuclear clearing histology
Anaplastic oligodendroglioma, IDH-mutant, 1p/19q codeleted (WHO grade III)

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

High Grade Glioma

Prognostic Factors

The data from the pre-IDH era indicated a poorer prognosis associated w/ the following factors:
  • >40 y/o (most sig. unfavorable factor)
  • Hx of astrocytoma
  • SOL ≥6 cm
  • Crossing the midline
  • Preexisting deficit preQx
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