Test ID: FCHIC
CHIC2, 4q12 Deletion (FIP1L1 and PDGFRA Fusion), FISH
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
Providing diagnostic genetic information for patients with hypereosinophilic syndrome (HES) and systemic mast cell disease (SMCD) involving CHIC2 deletion
Establishing the percentage of neoplastic interphase nuclei for patients with HES and SMCD at diagnosis and during treatment
Monitoring response to therapy
Method Name A short description of the method used to perform the test
Fluorescence In Situ Hybridization (FISH)
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
Eosinophilia
FIP1L1 gene
FIP1L1-PDGFRA kinase
Hypereosinophilia
Mast cell disease
Mastocytosis
MPD
Myeloproliferative disorder
PDGFRA gene
SMCD
Systemic mast cell disease
HES (Hypereosinophilia)
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.
Provide a reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.
Forms: If not ordering electronically, submit a Cytogenetics Hematologic Disorders Request Form (Supply T607) with the specimen.
Advise Express Mail or equivalent if not on courier service.
Submit only 1 of the following specimens:
Specimen Type: Blood
Container/Tube: Green top (sodium heparin)
Specimen Volume: 7-10 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Other anticoagulants are not recommended and are harmful to the viability of the cells.
Specimen Type: Bone marrow
Container/Tube: Green top (sodium heparin)
Specimen Volume: 1-2 mL
Collection Instructions:
1. Invert several times to mix bone marrow.
2. Other anticoagulants are not recommended and are harmful to the viability of the cells.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | Clotted blood or bone marrow |
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
Imatinib mesylate (Gleevec), a small molecule tyrosine kinase inhibitor from the 2-phenylaminopyrimidine class of compounds, has shown activity in the treatment of malignancies that are associated with the constitutive activation of a specific subgroup of tyrosine kinases. A novel tyrosine kinase, generated from fusion of the Fip1-like 1 (FIP1L1) gene to the PDGFRA gene, was identified in 9 of 16 patients (56%) with hypereosinophilic syndrome (HES). This fusion results from an approximate 800 kb interstitial chromosomal deletion that includes the cysteine-rich hydrophobic domain 2 (CHIC2) locus at 4q12. FIP1L1-PDGFRA is a constitutively activated tyrosine kinase that transforms hematopoietic cells, and is a therapeutic target for imatinib in a subset of HES patients.
Mast cell disease (MCD) is a clinically heterogeneous disorder wherein accumulation of mast cells (MC) may be limited to the skin (cutaneous mastocytosis) or involve 1 or more extra-cutaneous organs (systemic MCD [SMCD]). SMCD is often associated with eosinophilia (SMCD-eos). We recently tested the therapeutic activity of imatinib in 12 adults with SMCD-eos. In this study, we demonstrated that FIP1L1-PDGFRA is the therapeutic target of imatinib in the specific subset of patients with SMCD-eos. Furthermore, we provided evidence that the CHIC2 deletion is a surrogate marker for the FIP1L1-PDGFRA fusion.
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.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range.
Detection of an abnormal clone is usually associated with hypereosinophilic syndrome or systemic mastocytosis associated with eosinophilia.
The absence of an abnormal clone does not rule out the presence of neoplastic disorder.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test does not rule out cytogenetic or molecular genetic anomalies other than those specifically associated with CHIC2 deletion or insertional translocation.
Supportive Data
This method accurately detects deletion of CHIC2 and translocations involving the CHIC2 locus. We investigated a consecutive series of adult patients seen at Mayo Clinic with moderate or severe eosinophilia (median absolute eosinophil count of 4.1 x 10(9)/L, range 1.5-126.8/L). Bone marrow specimens were processed for FISH using standard methods. The FISH methodology was validated in 30 normal bone marrow and peripheral blood controls. Results of this study are in Pardanani A, Brockman SR, Paternoster SF, et al: F1P1L1-PDGFRA fusion: Prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosiniphilia. Blood 104:3038-3045, 2004)
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Pardanani A, Ketterling RP, Brockman SR, et al: CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood Nov 1 2003;102(9):3093-3096
2. Pardanani A, Brockman SR, Paternoster SF, et al: F1P1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosiniphilia. Blood 2004;104:3038-3045
3. Cools J, DeAngelo DJ, Gotlib J, et al: A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med Mar 2003;348(13):1201-1214
Method Description Describes how the test is performed and provides a method-specific reference
CHIC2 deletion studies can be performed on 1.0 mL of bone marrow aspirate or 10 mL of blood drawn into sodium heparin. DNA probes that map to FIP1L1, CHIC2, and PDGFRA at 4q12, hybridize to the chromosomes of cells from bone marrow or peripheral blood. These probes are visualized by fluorescent microscopy. Normal metaphase and interphase cells have 2 green/red/aqua fusion signals signifying the hybridization of the F1P1L1, CHIC2 and PDGFRA probes, respectively, to both chromosomes 4 at band 4q12. Cells with del(4)(q12) have 1 green/aqua fusion signal from the deleted chromosome 4 deletion of CHIC2) and 1 red/green/aqua fusion signal from the normal chromosome 4 at 4q12. Cells with ins(var;4)(var;q12) have 1 green/aqua fusion from the abnormal chromosome 4, 1 red on the insertional translocation recipient chromosome and 1 green/red/aqua fusion signal from the normal chromosome 4 at 4q12. Cells with translocations involving PDGRFA have 1 red/green fusion signal on the abnormal chromosome 4, 1 aqua signal on the translocation recipient chromosome and 1 green/red/aqua signal on the normal chromosome 4.
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.
Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m. CST.
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.
88271 x 3-DNA probe, each
88275 x 2-Interphase in situ hybridization
88291-Interpretation and report
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 |
|---|---|---|
| 84308 | Specimen | 31208-2 |
| 22461 | Specimen ID | N/A |
| G_681 | Source | N/A |
| 22463 | Order Date | N/A |
| G_683 | Reason For Referral | 42349-1 |
| 22465 | Method | In Process |
| 22466 | Results | 41749-3 |
| 22467 | Interpretation | 69965-2 |
| 22468 | Amendment | In Process |
| 22469 | Consultant | N/A |
| 22470 | Report Date | N/A |
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