PDGFRA, Mutation Analysis, Exon 12
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Several tumors can harbor KIT mutations, including gastrointestinal stromal tumors (GIST), mast cell disease, melanoma, seminoma, acute myeloid leukemia, myeloproliferative neoplasms, and lymphomas. In addition, occasional cases of GIST can also harbor mutations in PDGFRA, a gene structurally related to KIT, responsible for the expression of platelet derived growth factor receptor A. The frequency and type of mutations vary among these tumors and portent distinct clinical implications. The ordering physician is responsible for the diagnosis and management of disease and decisions based on the data provided.
Diagnosis and management of patients with gastrointestinal stromal tumors or other related tumors
Identification of a mutation in exon 12 of the PDGFRA gene
Results are reported as positive, negative, or failed. A negative result does not rule out the presence of a mutation.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Reliable results are dependent on adequate specimen collection and processing. This test has been validated on formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause PCR failure. False-negative results may occur in heterozygous tumor specimens when tumor cells comprise <60% of the cell population. Tumor cells are routinely enriched by macrodissection to avoid false-negative results.
PDGFRA mutations may be occasionally found in inflammatory fibroid polyps.(1)
Clinical diagnosis and therapy should not be based solely on this assay. The results should be considered in conjunction with clinical information, histologic evaluation, and additional diagnostic tests.
This test is unable to distinguish between a somatic and a germline KIT (or PDGFRA) mutation. Germline KIT (or PDGFRA) mutations are rare and their clinical relevance has been described in more detail in Clinical References 2 and 3. Testing of a peripheral blood specimen from this individual would be required to distinguish a germline from a somatic mutation. This test is not currently offered at Mayo Clinic.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Schildhaus HU, Cavlar T, Binot E, et al: Inflammatory fibroid polyps harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene. J Pathol 2008;216(2):176-182
2. Robson ME, Blogowski E, Sommer G, et al: Pleomorphic characteristics of a germ-line KIT mutation in a large kindred with gastrointestinal stromal tumors, hyperpigmentation, and dysphagia. Clin Cancer Res 2004;10:1250-1254
3. Li FP, Fletcher JA, Heinrich MC, et al: Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. J Clin Oncol 2005;23:2735-2743
4. Corless CL, Fletcher JA, Heinrich MC: Biology of gastrointestinal stromal tumors. J Clin Oncol 2004;22:3813-3825
5. Debiec-Rychter M, Raf Sciot R, Le Cesne A, et al: KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumors. Eur J Cancer 2006;42:1093-1103
6. Heinrich MC, Corless CL, Demetri GD, et al: Kinase mutations and imatinib mesylate response in patients with metastatic gastrointestinal stromal tumor. J Clin Onc 2003;21:4342-4349
7. Debiec-Rychter M, Dumez H, Judson I, et al: Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumors entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2004;40:689-695