Test Id : COGTF

This test is only performed on specimens from pediatric patients being considered for enrollment in a Children's Oncology Group (COG) protocol.

The fluorescence in situ hybridization (FISH) panel includes testing for the following abnormalities using the FISH probes listed:

+9/9p-, CDKN2A/D9Z1

t(9;22) or ABL1 amplification, ABL1/BCR

11q23 rearrangement, MLL (KMT2A) break-apart

-17/17p-, TP53/D17Z1

t(5;14), TLX3/BCL11B fusion

7q34 rearrangement, TRB break-apart

14q11.2 rearrangement, TRAD break-apart

t(10;11), MLLT10/PICALM fusion

1p33 rearrangement, TAL1/STIL

When an MLL (KMT2A) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:

t(11;19)(q23;p13.3) MLL/MLLT1

t(6;11)(q27;q23) MLLT4(AFDN)/MLL

t(4;11)(q21;q23) AFF1/MLL

t(9;11)(p22;q23) MLLT3/MLL

t(10;11)(p12;q23) MLLT10/MLL

t(11;19)(q23;p13.1) MLL/ELL

When a TRAD rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:

t(11;14)(p15;q11.2) LMO1/TRAD

t(8;14)(q24.1;q11.2) MYC/TRAD

t(10;14)(q24;q11.2) TLX1(HOX11)/TRAD

t(11;14)(p13;q11.2) LMO2/TRAD

When a TRB rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:

t(7;10)(q34;q24) TRB/TLX1

t(7;11)(q34;p15) TRB/LMO1

t(7;11)(q34;p13) TRB/LMO2

t(6;7)(q23;q34) MYB/TRB

In the absence of BCR/ABL1 fusion or apparent episomal ABL1 amplification, when an extra ABL1 signal is identified, reflex testing will be performed using the ABL1 break-apart probe set to evaluate for the presence or absence of an ABL1 rearrangement.

This test is only performed on specimens from pediatric patients being considered for enrollment in a Children's Oncology Group (COG) protocol. If this test is ordered and the laboratory is informed that the patient is not on a COG protocol, this test will be canceled and automatically reordered by the laboratory as TALPF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric Varies.

At follow-up, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and targeted T-ALL FISH probes can be evaluated based on the abnormalities identified in the diagnostic study. Order TALMF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies and request specific probes or abnormalities.

If the patient clinically relapses, a conventional chromosome study is useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.

For patients with T-cell lymphoma, order TLPDF / T-Cell Lymphoma, Diagnostic FISH, Varies.

For testing paraffin-embedded tissue samples from patients with T-cell lymphoblastic lymphoma, order TLBLF / T-Lymphoblastic Leukemia/Lymphoma, FISH, Tissue.

At diagnosis, conventional cytogenetic studies (COGBM / Chromosome Analysis, Hematologic Disorders, Children's Oncology Group Enrollment Testing, Bone Marrow) and this panel should be performed. If there is limited specimen available, only this test will be performed.

Advise Express Mail or equivalent if not on courier service.

1. A reason for testing, a flow cytometry and/or a bone marrow pathology report, and a Children's Oncology Group (COG) registration number and protocol number should be submitted 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. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

2. If the patient has received an opposite sex bone marrow transplant, note this information on the request.

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 to 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.

Acceptable

Specimen Type: Blood

Container/Tube:

Preferred: Yellow top (ACD)

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

Specimen Volume: 6 mL

Collection Instructions: Invert several times to mix blood.

If not ordering electronically, complete, print, and send a Children's Oncology Group Test Request (T829) with the specimen.

Blood: 2 mL

Bone Marrow: 1 mL

Evaluation of pediatric bone marrow and peripheral blood specimens by fluorescence in situ hybridization probe analysis for classic rearrangements and chromosomal copy number changes associated with T-cell acute lymphoblastic leukemia in patients being considered for enrollment in Children's Oncology Group clinical trials and research protocols

This test is only performed on specimens from pediatric patients being considered for enrollment in a Children's Oncology Group (COG) protocol.

The fluorescence in situ hybridization (FISH) panel includes testing for the following abnormalities using the FISH probes listed:

+9/9p-, CDKN2A/D9Z1

t(9;22) or ABL1 amplification, ABL1/BCR

11q23 rearrangement, MLL (KMT2A) break-apart

-17/17p-, TP53/D17Z1

t(5;14), TLX3/BCL11B fusion

7q34 rearrangement, TRB break-apart

14q11.2 rearrangement, TRAD break-apart

t(10;11), MLLT10/PICALM fusion

1p33 rearrangement, TAL1/STIL

When an MLL (KMT2A) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:

t(11;19)(q23;p13.3) MLL/MLLT1

t(6;11)(q27;q23) MLLT4(AFDN)/MLL

t(4;11)(q21;q23) AFF1/MLL

t(9;11)(p22;q23) MLLT3/MLL

t(10;11)(p12;q23) MLLT10/MLL

t(11;19)(q23;p13.1) MLL/ELL

When a TRAD rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:

t(11;14)(p15;q11.2) LMO1/TRAD

t(8;14)(q24.1;q11.2) MYC/TRAD

t(10;14)(q24;q11.2) TLX1(HOX11)/TRAD

t(11;14)(p13;q11.2) LMO2/TRAD

When a TRB rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:

t(7;10)(q34;q24) TRB/TLX1

t(7;11)(q34;p15) TRB/LMO1

t(7;11)(q34;p13) TRB/LMO2

t(6;7)(q23;q34) MYB/TRB

In the absence of BCR/ABL1 fusion or apparent episomal ABL1 amplification, when an extra ABL1 signal is identified, reflex testing will be performed using the ABL1 break-apart probe set to evaluate for the presence or absence of an ABL1 rearrangement.

In the United States, the incidence of acute lymphoblastic leukemia (ALL) is roughly 6000 new cases per year (as of 2019). ALL accounts for approximately 70% of all childhood leukemia cases (ages 0 to 19 years), making it the most common type of childhood cancer.

Approximately 85% of pediatric cases of ALL are B-cell lineage (B-ALL) and 15% are T-cell lineage (T-ALL). T-ALL is more common in adolescents than younger children and accounts for 25% of adult ALL. When occurring as a primary lymphoblastic lymphoma (LBL), approximately 90% are T-cell lineage versus only 10% B-cell lineage. T-LBL often present as a mediastinal mass in younger patients with or without concurrent bone marrow involvement.

Specific genetic abnormalities are identified in the majority of cases of T-ALL, although many of the classic abnormalities are "cryptic" by conventional chromosome studies and must be identified by fluorescence in situ hybridization (FISH) studies. Each of the genetic subgroups are important to detect and can be critical prognostic markers. One predictive marker, amplification of the ABL1 gene region, has been identified in 5% of T-ALL, and these patients may be responsive to targeted tyrosine kinase inhibitors.

A combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients to characterize the T-ALL clone for the prognostic genetic subgroups. A summary of the characteristic chromosome abnormalities identified in T-ALL are listed in the following table.

Table. Common Chromosome Abnormalities in T-cell Acute Lymphoblastic Leukemia

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 neoplastic disorder.

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

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

Bone marrow is the preferred specimen type for this FISH test. If bone marrow is not available, a blood specimen may be used if there are malignant 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.

1. Swerdlow SH, Campo E, Harris NL, et al, eds: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press; 2017

2. Gesk S, Martin-Subero JI, Harder L, et al: Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci. Leukemia. 2003;17:738-745

3. Chin M, Mugishima H, Takamura M, et al: Hemophagocytic syndrome and hepatosplenic (gamma)(delta) T-cell lymphoma with isochromosome 7q and 8 trisomy. J Pediatr Hematol Oncol. 2004;26(6):375-378

4. Graux C, Cools J, Michaux L, et al: Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia. 2006;20:1496-1510

5. Liu Y, Easton J, Shao Y, et al: The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017;49(8):1211-1218

This test is performed using commercially available and laboratory-developed probes. Deletion of the CDKN2A locus on chromosome 9 and TP53 on chromosome 17 are detected using enumeration strategy probes. Rearrangements involving TAL1/STIL, TRB, MLL (KMT2A), and TRAD are detected using dual-color break-apart (BAP) strategy probes. Dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) strategy probe sets are used to detect t(5;14), t(9;22), t(10;11), and in reflex testing when rearrangements of MLL, TRB, or TRAD genes are detected. Amplification of the ABL1 (9q34) is detected using a D-FISH probe strategy. 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 x2, 88275 x1, 88291 x1- FISH Probe, Analysis, Interpretation; 1 probe set

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