Gastrointestinal stromal tumour focused gene panel

Also known as: GIST panel, KIT, PDGFRA, BRAF

Test category:

Oncology – Gastrointestinal stromal tumours

Use of test

Purpose:

Gastrointestinal stromal tumours (GISTs) are characterised by the presence of activating mutations in either KIT or PDGFRA. The specific mutation may have implications regarding use of KIT tyrosine kinase inhibitor therapy in the adjuvant or metastatic setting.

A small percentage of GISTs do not have mutations in KIT or PDGFRA (‘wild-type’ GISTS). Wild-type GISTs may have mutations in BRAF (among other genes, such as NF1 and the SDH genes). Presence of a BRAF mutation is associated with resistance to KIT tyrosine kinase inhibitors.

 

Utility:

The specific KIT or PDGFRA mutation may have implications in terms of prognosis and the type/dosage of KIT tyrosine kinase inhibitor (TKI) therapy. Access to TKI therapy via the PBS depends on KIT expression, determined by positive immunohistochemistry (CD117 staining). Detection of a KIT or PDGFRA mutation may be useful if CD117 immunohistochemistry is uninformative. In addition, certain mutations can be associated with resistance to TKIs - either as a primary mutation (e.g. PDGFRA D842V), or arising as a secondary resistance mechanism.

Optimal systemic therapy for “wild-type” GISTs (with no KIT or PDGFRA mutation) is an area of active investigation, and such patients may be eligible for clinical trials. There has been at least one case report of a patient with a BRAF V600E mutation and clinical response to the BRAF TKI dabrafenib.

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, KIT and PDGFRA mutations have been reported in rare cases of familial GIST. Such mutations would be detected by this assay, but would not be differentiated from a somatic mutation. If a familial KIT or PDGFRA mutation is suspected on clinical grounds, referral to a Clinical Genetics service or Familial Cancer Centre is recommended.

Methodology:

Targeted analysis of clinically relevant activating mutations in BRAF (codon V600), KIT (exons 9, 11, 13, 17) and PDGFRA (exons 12 and 18). This assay detects targeted single nucleotide variants and insertion/deletion mutations (of up to 24 base pairs in size). KIT in particular harbours a number of large insertion/deletion mutations, and approximately 15% of KIT indels will not be detected by this assay. 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:

No MBS rebate is available for the GIST focused panel.

 

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