Familial Gastrointestinal Stromal Tumors (GISTs) via the PDGFRA Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code TestIndividual Gene PriceCPT Code Copy CPT Codes
1201 PDGFRA$1280.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Approximately 90% of individuals with Familial GISTS will have a mutation in the KIT and PDGFRA genes. PDGFRA causative mutations are found in approximately 1/3 of patients who test negative for KIT mutations (Antonescu. Seminars in Diagnostic Pathology 23:63-69, 2006).

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Deletion/Duplication Testing via aCGH

Test Code TestIndividual Gene PriceCPT Code Copy CPT Codes
600 PDGFRA$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Features

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors found in the gastrointestinal tract. In most cases, GISTs spontaneously arise due to somatic mutations in the KIT gene, and less frequently in the PDGFRA gene. Families with GISTs and germline mutations in the KIT and PDGFRA genes have been described. Familial GISTs are often distinct from sporadic GISTs in that they are multiple in number, smaller in size, and present hyperplasia of interstitial cells of Cajal (ICC). Individuals with PDGFRA mutations show clinical manifestations similar to patients with KIT germline mutations, including dysphagia, hyperpigmentation and urticaria pigmentosa; however patients with germline PDGFRA mutations have distinct clinical features, such as large hands, lipomas, intestinal neurofibromatosis, and small intestine fibrous tumors. (Postow and Robson. Clinical Sarcoma Research 2:16, 2012) . In addition, patients with a germline PDGFRA mutation appear to have better outcomes compared to individuals with KIT germline mutations (Maleddu et al. Journal of Translational Medicine 9:75, 2011; Antonescu. Seminars in Diagnostic Pathology 23:63-69, 2006). Interestingly, individuals who are positive for either KIT and PDGFRA tumor mutations are treated with Imatinib, a KIT and PDGFRA inhibitor, which has been successfully used in the treatment of metastatic GISTs (Lasota and Miettinen. Histopathology 53, 245–266, 2008). Other diseases in which germline PDGFRA mutations are present include Hypereosinophilic syndrome, Vitiligo vulgaris, and isolated cleft palate.


Familial GISTs are inherited as an autosomal dominant disease caused by mutations in KIT and PDGFRA. While the majority of mutations are found in the KIT gene, several families have been found to have causative mutations in the PDGFRA gene.  PDGFRA encodes a trans-membrane receptor that belongs to the type III tyrosine kinase family whose natural ligands are stem cell factor (SCF) and platelet derived growth factor (Maleddu et al., 2011). Ligand binding promotes autophosphorylation of the PDGRA receptor and activation of downstream targets, such as the Ras/MAP kinase, Rac/Rho-JNK, PI3K/AKT, and SFK/STAT signaling networks (Antonescu, 2006). These pathways are involved in cellular differentiation and growth. Deregulation leads to tumorigenesis.  The majority of causative germline mutations in the PDFRA gene are missense mutations, and are mostly similar to those found in sporadic GISTs (Lasota and Miettinen, 2008). No consistent genotype-phenotypes correlations exist for Familial GISTs.

Testing Strategy

The platelet-derived growth factor receptor alpha is encoded by 22 exons (2-23) from the PDGFRA gene on chromosome 4q12.  Testing is accomplished by amplifying each coding exon and ~20 bp of adjacent noncoding sequence, then determining the nucleotide sequence using standard dideoxy Sanger sequencing methods and a capillary electrophoresis instrument. We will also sequence any single exon (Test #100) in family members of patients with a known mutation or to confirm research results.

Indications for Test

Candidates for this test are patients with a history of familial GISTs, and especially those who have tested negative for KIT germline mutations. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue. This test can also be used for testing PDGFRA mutation status in Hypereosinophilic syndrome, Vitiligo vulgaris, and isolated cleft palate.


Official Gene Symbol OMIM ID
PDGFRA 173490
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Genetic Counselors
  • Antonescu. (2006). "Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models." Seminars in Diagnostic Pathology 23:63-69. PubMed ID: 17193819
  • Lasota and Miettinen. (2008). "Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours." Histopathology 53, 245–266. PubMed ID: 18312355
  • Maleddu et al. (2011). "The role of mutational analysis of KIT and PDGFRA in gastrointestinal stromal tumors in a clinical setting." Journal of Translational Medicine 9:75. PubMed ID: 21605429
  • Postow and Robson. (2012). "Inherited gastrointestinal stromal tumor syndromes: mutations, clinical features, and therapeutic implications." Clinical Sarcoma Research 2:16,. PubMed ID: 23036227
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • The first four pages of the requisition form must accompany all specimens.
  • Billing information is on the third and fourth pages.
  • Specimen and shipping instructions are listed on the fifth and sixth pages.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3-5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10-20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is good for up to 48 hours.
  • If refrigerated, blood specimen is good for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • NextGen Sequencing Tests: Send in screw cap tube at least 10 µg of purified DNA at a concentration of at least 50 µg/ml
  • Sanger Sequencing Tests: Send in a screw cap tube at least 15 µg of purified DNA at a concentration of at least 20 µg/ml. For tests involving the sequencing of more than three genes, send an additional 5 µg DNA per gene. DNA may be shipped at room temperature.
  • Deletion/Duplication via aCGH: Send in screw cap tube at least 1 µg of purified DNA at a concentration of at least 100 µg/ml.
  • Whole-Genome Chromosomal Microarray: Collect at least 5 µg of DNA in TE (10 mM Tris-cl pH 8.0, 1mM EDTA), dissolved in 200 µl at a concentration of at least 100 ng/ul (indicate concentration on tube label). DNA extracted using a column-based method (Qiagen) or bead-based technology is preferred.


(Delivery accepted Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Ship at least two T25 flasks of confluent cells.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We do not culture cells.