Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas

Patient Guideline Summary

Publication Date: February 16, 2022

Last Updated: November 29, 2023

Objective

This patient summary means to discuss key recommendations from the College of American Pathologists in collaboration with the American Association of Neuropathologists, Association for Molecular Pathology, and Society for Neuro-Oncology for molecular biomarker testing for the diagnosis of diffuse gliomas.

Overview

Diffuse glioma is a brain and spinal cord cancer that intertwines (mixes in) with normal nerve cells, making it impossible to remove with surgery.
We will use the abbreviation DG throughout this summary to refer to diffuse gliomas.
Symptoms reflect the part of the nervous system involved.
These tumors affect patients of all ages. They are caused by genetic mutations.
Each mutation is assigned a specific name using letters/numbers as abbreviations to make it easier for healthcare providers and scientists to talk about them. You do not need to know the full name of the mutations, but it is important to find out if you have any.
To identify which mutation you have, your care team will test for “biomarkers.”
Biomarkers are special entities in your body that “mark” the presence of certain characteristics or diseases. They provide valuable information about your cancer and how it may respond to certain medications.
This patient summary focuses on testing to characterize each individual case.

Diagnosis

The nature of DGs varies greatly. Therefore, the course of the disease and its treatment also vary.
Molecular testing identifies abnormal genes and gene products (proteins)
- Molecular testing must be done on all DGs.
- Molecular testing requires a small biopsy specimen.
- Testing is sequential; each test result leads to another until a final diagnosis is reached.

Here is the testing according to the cancer type:

For all DG:
- Isocitrate dehydrogenase (IDH) mutational testing
For all IDH-mutant DG:
- ATRX chromatin remodeler (ATRX) status (unless they show 1p/19q codeletion)
- Tumor protein p53 (TP53) status (unless they show 1p/9q codeletion)
- 1p/19q codeletion testing (unless they show ATRX loss or TP53 mutations)
For IDH-mutant astrocytomas:
- Cyclin-dependent kinase inhibitor 2A (CDKN2A)/cyclin-dependent kinase inhibitor 2B (CDKN2B) homozygous deletion testing
For Glioblastoma (GBM), IDH-wild type (WT):
- O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation testing
For Oligodendroglioma and IDH-WT GBM:
- TERT promoter mutation testing
For Histologic Grade 2-3 DG, IDH-WT (to establish the molecular diagnosis of GBM, IDH-WT, grade 4):
- Whole chromosome 7 gain/whole chromosome 10 loss testing
- Epidermal growth factor receptor (EGFR) amplification testing
- Telomerase reverse transcriptase (TERT) promoter mutation testing
For DG Involving the Midline:
- Histone 3 (H3) K27M testing
For Pediatric and Young Adult Patients with IDH-WT DG:
- H3 G34 testing
For DG that are IDH-WT and H3-WT:
- B-Raf proto-oncogene (BRAF) mutation testing (V600)
For Children and Young Adults with Histologic Grade 2-3 DG that are IDH-WT:
- MYB proto-oncogene (MYB)/MYB-like (MYBL1) and fibroblast growth factor receptor 1 (FGFR1) testing

Abbreviations

DG: Diffuse Glioma

Source Citation

Brat DJ, Aldape K, Bridge JA, Canoll P, Colman H, Hameed MR, Harris BT, Hattab EM, Huse JT, Jenkins RB, Lopez-Terrada DH, McDonald WC, Rodriguez FJ, Souter LH, Colasacco C, Thomas NE, Yount MH, van den Bent MJ, Perry A. Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas. Arch Pathol Lab Med. 2022 Feb 17. doi: 10.5858/arpa.2021-0295-CP. Epub ahead of print. PMID: 35175291.

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.