Test ID: 89671
PDGFRA, Mutation Analysis, Exon 12
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Diagnosis and management of patients with gastrointestinal stromal tumors or other related tumors
Identification of a mutation in exon 12 of the PDGFRA gene
Additional Tests Lists test(s) that are always performed, at an additional charge, with the initial test(s)
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| 60254 | AP Special Studies Review | No | Yes |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
This test is performed in conjunction with AP special studies review. Additional testing may be performed after review by pathologist and AP special studies review could be changed to 5439 Surgical Pathology Consultation if they determine this is more appropriate and upon approval from the requesting clinician.
See Gastrointestinal Stromal Tumor (GIST) Testing Algorithm in Special Instructions.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Polymerase Chain Reaction (PCR) and Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Gastrointestinal Stromal Tumor
GIST
Mutation Screening
GST12
PDGFRA exon 12
PDGFRA ex 12
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
A pathology/diagnostic report including a brief history is required. If available, include KIT Immunostain results.
Specimen Type:
Preferred: Formalin-fixed, paraffin-embedded (FFPE) tissue block with a minimum of 60% tumor cell population
Acceptable: Unstained slides with a minimum of 60% tumor population; slides may be stained and/or scraped
Collection Instructions:
1. Process all specimens into FFPE blocks prior to submission.
2. If submitting slides, a minimum of ten, 4- to 5-micron thick, unstained slides are required.
Additional Information:
1. A quality specimen is essential for evaluation. Submit only tissue containing tumor cells; minimal tissue is required for evaluation.
2. Special stains performed outside Mayo Medical Laboratories and included with the case may be repeated and charged at the reviewing pathologist's discretion. Testing requested by referring physician may not be performed if deemed unnecessary by Mayo Clinic pathologist.
Forms: If not ordering electronically, submit a Pathology/Cytology Request Form (Supply T246) with the specimen.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | Decalcified specimens |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Refrigerated | ||
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.
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.
Negative
Interpretation Provides information to assist in interpretation of the test results
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.
Supportive Data
We studied a set of 75 formalin-fixed, paraffin-embedded specimens: 40 classic gastrointestinal stromal tumors (GIST), 10 unrelated tumors, 21 neuroendocrine tumors, and 4 other tumors (2 metastatic melanomas, 1 breast cancer, and 1 squamous cell carcinoma). The literature reports that approximately 80% of GISTs harbor a mutation in KIT gene, while 2% to 5% harbor mutations in PDGFRA. Overall, we found 83% of GISTs tested demonstrated mutations in KIT and/or PDGFRA, which is in accordance with the literature.
Clinical Reference 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
Method Description Describes how the test is performed and provides a method-specific reference
The paraffin-embedded tissue is macroscopically examined and the tumor-rich portion is dissected, deparaffinized, lysed, and digested. Genomic DNA is extracted using either a phenol-chloroform method or the QIAamp DNA FFPE Tissue Kit (Qiagen). The DNA is amplified via PCR. Primers specific for PDGFRA exon 12 are used. Negative or wild-type and no template or water controls are used for each run. The patient and control samples are sent for direct DNA sequencing. The sequencing chromatograms are analyzed by manual and software methods and the presence or absence of a PDGFRA exon 12 mutation is determined. The results are interpreted and reported by a working group pathologist.(Qiagen DNA FFPE Tissue Handbook; Unpublished Mayo methods)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; 8 a.m.-5 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81404-PDGFRA (platelet-derived growth factor receptor alpha polypeptide) (eg, gastrointestinal stromal tumor), targeted sequence analysis (eg, exons 12, 18)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 89671 | PDGFRA, Mutation Analysis, Ex12 | In Process |
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