Glioma focused gene panel

Also known as: Glioma panel, BRAF, IDH1, IDH2, TP53

Test category:

Oncology – Gliomas

Use of test

Purpose:

IDH1 (at codon 132) or IDH2 (at codons 140 and 172) are commonly mutated in glial tumours. In addition to IDH1 and IDH2, the glioma panel tests for mutations in exons 4-9 of TP53, and BRAF mutations (predominantly V600E).

Additional molecular testing is available if required (e.g. 1p/19q co-deletion status by FISH in a putative oligodendroglioma; this test is also Medicare rebated).

 Utility:

The WHO classification system for diffuse astrocytic and oligodendroglial tumours requires testing for IDH1 and IDH2 mutations.

The most common IDH1 mutation can be detected by immunohistochemistry. If this is not present in a diffuse glioma, then molecular testing is required for other IDH1 and IDH2 mutations; such testing is rebated by Medicare.

IDH1/2 status may also have prognostic implications, with IDH1/2 mutant tumours typically having a better prognosis than “wild-type” tumours.

Presence of a TP53 mutation (and/or abnormal TP53 immunohistochemistry) supports a diagnosis of diffuse astrocytoma, as opposed to oligodendroglioma. TP53 mutations are also common in glioblastomas; in particular, secondary glioblastomas arising from a precursor astrocytoma.

Finally, the BRAF V600E mutation can be found in pleomorphic xanthoastrocytomas, gangliogliomas, some pilocytic astrocytomas, and defines a subset of IDH-wild type diffuse gliomas (typically seen in children or adolescents). Presence of a BRAF activating mutation may also offer options for clinical trials involving targeted therapy.

This test can be expanded to a full Find It panel that simultaneously evaluates the mutation status of tumour DNA at more than 140 well-characterised positions (hotspots) and more than 20 exons in no less than 30 cancer-associated genes.

 
Ethical considerations:

This assay is designed to detect non-heritable mutations. It does typically not raise issues of ethics or consent that are different from most other investigations ordered in the routine care of a patient. However, germline (inherited) TP53 mutations cause Li-Fraumeni syndrome (LFS). Such mutations would be detected by this assay, but would not be differentiated from a somatic mutation. If Li-Fraumeni syndrome is suspected on clinical grounds, referral to a Clinical Genetics service or Familial Cancer Centre is recommended.

Methodology:

Targeted analysis of clinically relevant mutations in IDH1 (codon 132), IDH2 (codons 140 and 172), BRAF (codon V600) and TP53 (exons 4 to 9). This assay detects targeted single nucleotide variants and insertion/deletion mutations (of up to 24 base pairs in size). Fusion genes and copy number variants will not be detected. Very low level targeted variants (<5% variant allele frequency) may not be detected.

For further details, please refer to the description of the full Find It panel.

Requesting the test

Ordering:

This test is usually requested by a surgeon or oncologist. Please use the specific request form (see link below).

Request Form:

Download the somatic mutation request form.

Sample required:

Formalin-fixed, paraffin embedded tissue (FFPE) - 15 sections of 4 uM thickness, dried overnight at 37°C onto charged/coated slides.

Special instructions:

Please label each slide with patient and block identifiers plus number them sequentially 1-15. Stain slides 1 and 15 with H&E and leave slides 2 to 14 unstained. The request should be accompanied by the somatic mutation request form (above) and a copy of the original histopathology report.

Turnaround time:

7 business days from receipt of sections by the testing laboratory.

Price:

$350.

Rebate:

An MBS rebate is available for the glioma focussed panel, if criteria are met (73372). There is also a rebate for 1p/19q co-deletion testing by FISH, if criteria are met (73371).

 

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