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Gastrointestinal Stromal Tumors (GISTs), PDGFRA Mutation Analysis
- Tyrosine Kinase Inhibitor (TKI, Imatinib) Responsiveness
The platelet-derived growth factor receptor alpha (PDGFRA) gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. PDGFRA and c-KIT have approximately 35% homology. They both belong to the PDGFRA subfamily of receptor tyrosine kinases, which are involved in the regulation of cell growth, proliferation, adhesion, migration, differentiation, and apoptosis.
Genomic DNA is purified from the specimen provided. Exons 10, 12, 14, and 18 of PDGFRA gene coding are subjected to PCR amplification and bidirectional sequencing in duplicate to identify sequence variations. This assay has a sensitivity to detect approximately 10% of cells containing the PDGFRA mutations in a background of nonmutant cells. This assay will not detect the mutation below the sensitivity of this assay.
This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary.
Polymerase chain reaction (PCR) and DNA sequencing
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract, located mostly in the stomach (60%) and small intestine (35%). Approximately 80% of GISTs have a mutation in c-KIT and 5% to 10% of GISTs have a mutation in PDGFRA. PDGFRA mutations are mutually exclusive with c-KIT mutations but active similar signal transduction pathways that support GIST oncogenesis. The location of c-KIT and PDGFRA mutations in GISTs is associated with the site of origin, histological phenotype, and treatment response to tyrosine kinase inhibitors (TKI, such as imatinib and sunitinib). Patients with mutations in c-KIT exon 11 have been shown to have significantly better response rates to imatinib treatment when compared with patients who have the c-KIT exon 9 mutations or no mutation. Patients with mutations in c-KIT exon 9 may benefit from dose escalation depending on tolerance. Secondary mutations usually occur in c-KIT kinase domains in patients after imatinib treatment resulting in resistance to this drug. Other TKI inhibitors, such as sunitinib and sorafenib, could be used as a replacement drug for selected mutations. Most known mutations in the PDGFRA gene are associated with imatinib response with the exception of D842V mutation. In a subset of intestinal high-risk GISTs lacking c-KIT/PDGFRA mutations, 7% have a mutation in BRAF. Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset.
Formalin-fixed, paraffin-embedded (FFPE) tissue or five unstained slides from a paraffin block in 10-μM sections and a matching H&E reference slide
Formalin-fixed, paraffin-embedded (FFPE) block or five unstained slides from paraffin block in 10-μM sections and a matching H&E reference slide
2 mm x 2 mm tumor area with ≥50% tumor
Maintain blocks and slides at room temperature.
Causes for Rejection
Tumor block containing insufficient tumor tissue or tumor fixed in a heavy metal fixative; broken or stained slides
Please provide a copy of the pathology report, and direct any questions regarding this test to oncology customer service at 800-345-4363.
|Order Code||Order Code Name||Order Loinc||Result Code||Result Code Name||UofM||Result LOINC|
|510860||PDGFRA Analysis in GISTs||510861||Mutation Analysis Result:||41103-3|
|510860||PDGFRA Analysis in GISTs||510862||Nucleotide Change||48004-6|
|510860||PDGFRA Analysis in GISTs||510863||Amino Acid Change:||48005-3|
|510860||PDGFRA Analysis in GISTs||510869||Block Number:||N/A|
|510860||PDGFRA Analysis in GISTs||510864||Background:||77202-0|
|510860||PDGFRA Analysis in GISTs||510868||Clinical Significance||N/A|
|510860||PDGFRA Analysis in GISTs||510865||Methodology:||49549-9|
|510860||PDGFRA Analysis in GISTs||510866||References:||75608-0|
|510860||PDGFRA Analysis in GISTs||510867||Director Review:||72486-4|
|510860||PDGFRA Analysis in GISTs||480903||Microdissection Performed||8100-0|