Test Id : EOSDF

This test includes a charge for the probe application, analysis, and professional interpretation of results for 5 probe sets (11 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.

The panel includes testing for the following kinase activating chromosome abnormalities, using the following FISH probes:

4q12 deletion or rearrangement, FIP1L1, CHIC2 ,PDGFRA

5q32 rearrangement, PDGFRB

8p11.2 rearrangement, FGFR1

9p24.1 rearrangement, JAK2

9q34 rearrangement, ABL1

In the absence of a CHIC2 deletion, if an extra or atypical CHIC2 or PDGFRA signal is identified, reflex testing will be performed using the PDGFRA break-apart probe set to evaluate for the presence or absence of a PDGFRA rearrangement.

If a PDGFRB rearrangement is identified, reflex testing using the PDGFRB/ETV6 probe set will be performed to evaluate for the presence or absence of t(5;12)(q32;p13) -PDGFRB/ETV6 fusion.

If an ABL1 rearrangement is identified, reflex testing using the ABL1/BCR probe set will be performed to evaluate for the presence or absence of t(9;22)(q34;q11.2) - ABL1/BCR fusion.

This test is intended to be ordered when the entire chronic eosinophilia fluorescence in situ hybridization (FISH) panel is needed.

A reason for testing and a flow cytometry and/or a bone marrow pathology report should be submitted with each specimen. The laboratory will not reject testing if this information is not provided however, appropriate testing and interpretation may be compromised or delayed. If not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

Submit only 1 of the following specimens:

Preferred

Specimen Type: Bone marrow

Container/Tube:

Preferred: Yellow top (ACD)

Acceptable: Green top (heparin) or lavender top (EDTA)

Specimen Volume: 2-3 mL

Collection Instructions:

1. It is preferable to send the first aspirate from the bone marrow collection.

2. Invert several times to mix bone marrow.

3. Send bone marrow specimen in original tube. Do not aliquot.

Acceptable

Specimen Type: Blood

Container/Tube:

Preferred: Yellow top (ACD)

Acceptable: Green top (heparin) or lavender top (EDTA)

Specimen Volume: 6 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Blood: 2 mL

Bone Marrow: 1 mL

Detecting a neoplastic clone associated with the common chromosome abnormalities seen in patients with myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement (including PDGFRA, PDGFRB, FGFR1, JAK2, and ABL1).

Supporting the diagnosis of malignancy if a clone is present

An adjunct to conventional chromosome studies.

This test includes a charge for the probe application, analysis, and professional interpretation of results for 5 probe sets (11 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.

The panel includes testing for the following kinase activating chromosome abnormalities, using the following FISH probes:

4q12 deletion or rearrangement, FIP1L1, CHIC2 ,PDGFRA

5q32 rearrangement, PDGFRB

8p11.2 rearrangement, FGFR1

9p24.1 rearrangement, JAK2

9q34 rearrangement, ABL1

In the absence of a CHIC2 deletion, if an extra or atypical CHIC2 or PDGFRA signal is identified, reflex testing will be performed using the PDGFRA break-apart probe set to evaluate for the presence or absence of a PDGFRA rearrangement.

If a PDGFRB rearrangement is identified, reflex testing using the PDGFRB/ETV6 probe set will be performed to evaluate for the presence or absence of t(5;12)(q32;p13) -PDGFRB/ETV6 fusion.

If an ABL1 rearrangement is identified, reflex testing using the ABL1/BCR probe set will be performed to evaluate for the presence or absence of t(9;22)(q34;q11.2) - ABL1/BCR fusion.

The myeloid/lymphoid neoplasms with eosinophilia and rearrangements of PDGFRA, PDGFRB, FGFR1 and JAK2 represent a significantly diverse group of hematologic malignancies. Despite the disparate clinical presentations, which include chronic myeloid neoplasms (chronic myelomonocytic leukemia, chronic myeloproliferative neoplasms, chronic eosinophilic leukemia) versus more acute myeloid and lymphoid neoplasms (acute myeloid leukemia, B- and T-lymphoblastic leukemia/lymphoma and mixed phenotypic acute leukemias), this diagnostic subgroup shares rearrangements involving 4 specific gene regions: PDGFRA, PDGFRB, FGFR1, and JAK2.

While conventional chromosome studies may detect many of the rearrangements associated with these gene rearrangements, several are cytogenetically "cryptic," including the most common abnormality involving PDGFRA activation. This one megabase submicroscopic, intrachromosomal deletion results in loss of the CHIC2 gene region with subsequent fusion of neighboring genes FIP1L1 and PDGFRA. In addition to this more common, cryptic deletion, the PDGFRA gene has many translocation partners described (at least 15) that similarly result in PDGFRA upregulation.

The PDGFRB, FGFR1, and JAK2 gene regions similarly have numerous translocation/inversion partners described, at least 50 for PDGFRB, 10 for FGFR1, and 40 for JAK2. Despite the significant heterogeneity in gene partners, the identification of PDGFRA, PDGFRB, FGFR1, and JAK2 rearrangements is critical for disease categorization and potential therapeutic intervention. Both PDGFRA and PDGFRB have the potential for response to targeted tyrosine kinase inhibitor therapies such as imatinib mesylate. Similarly, JAK2 rearrangements have the potential for response to targeted inhibitor therapy. Rearrangements of FGFR1 are typically more aggressive and less responsive to targeted inhibitors.

While not formally included in the World Health Organization categorization of myeloid/lymphoid neoplasms with PDGFRA, PDGFRB, FGFR1, or JAK2 rearrangements, rearrangements of the ABL1 gene other than with the BCR locus, can result in similar clinical phenotypes. Thus, the ABL1 gene region has been included in this fluorescence in situ hybridization panel evaluation to appropriately interrogate this gene region, particularly since these patients may not be identified by conventional karyotype analysis and may significantly benefit from targeted tyrosine kinase therapies.

An interpretive report will be provided.

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe.

The absence of an abnormal clone does not rule out the presence of a neoplastic disorder.

This test is not approved by the US Food and Drug Administration, and it is best used as an adjunct to clinical and pathologic information.

Fluorescence in situ hybridization (FISH) is not a substitute for conventional chromosome studies because the latter detects chromosome abnormalities associated with other hematological disorders that would be missed by this FISH panel test.

Bone marrow is the preferred sample type for this FISH test. If bone marrow is not available, a blood specimen may be used if there are neoplastic cells in the blood specimen (as verified by a hematopathologist).

Each probe was independently tested and verified on unstimulated peripheral blood and bone marrow specimens. Normal cutoffs were calculated based on the results of 25 normal specimens. Each probe set was evaluated to confirm the probe set detected the abnormality it was designed to detect.

Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement. In: Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours. Vol 2.  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. IARC Press; 2017:71-80

This test is performed using commercially available and laboratory-developed probes. Rearrangements or deletions involving CHIC2, PDGFRA, PDGFRB, FGFR1, JAK2, and ABL1 are detected using a tri or dual-color break-apart (BAP) strategy probe. Dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) strategy probe sets are used in reflex testing when rearrangements of the PDGFRB and ABL1 gene are detected. For enumeration and BAP strategy probe sets, 100 interphase nuclei are scored; 200 interphase nuclei are scored when D-FISH probes are used. All results are expressed as the percent abnormal nuclei.(Unpublished Mayo method)

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This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

88271 x11, 88275 x5, 88291 x1-FISH Probe, Analysis, Interpretation; 5 probe sets

88271 x2, 88275 x1–FISH Probe, Analysis; each additional probe set (if appropriate)