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HelpTest ID: COGTF T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies
Ordering Guidance
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.
Additional Testing Requirements
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.
Shipping Instructions
Advise Express Mail or equivalent if not on courier service.
Necessary Information
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. Â 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.
Specimen Required
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.
Useful For
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
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| COGTB | Probe, Each Additional (COGTF) | No, (Bill Only) | No |
Testing Algorithm
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
Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.
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.
Method Name
Fluorescence In Situ Hybridization (FISH)
Reporting Name
COG, ALL (T-cell), FISHSpecimen Type
VariesSpecimen Minimum Volume
Blood: 2 mL
Bone Marrow: 1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Refrigerated | |||
Clinical Information
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
|
Cytogenetic change |
Genes involved |
|
del(1p33) |
TAL1/STIL |
|
t(5;14)(q35;q32) |
TLX3/BCL11B |
|
t(10;11)(p12;q14) |
MLLT10/PICALM |
|
Episomal amplification |
ABL1 |
|
del(9p) |
CDKN2A(p16) |
|
t(11q23;var) |
MLL(KMT2A) |
|
t(4;11)(q21;q23) |
AFF1/MLL(KMT2A) |
|
t(6;11)(q27;q23) |
MLLT4(AFDN)/MLL(KMT2A) |
|
t(9;11)(p22;q23) |
MLLT3/MLL(KMT2A) |
|
t(10;11)(p12;q23) |
MLLT10)/MLL(KMT2A) |
|
t(11;19)(q23;p13.1) |
MLL(KMT2A)/ELL |
|
t(11;19)(q23;p13.3) |
MLL(KMT2A)/MLLT1 |
|
t(7q34;var) |
TRB |
|
t(6;7)(q23;q34) |
MYB/TRB |
|
t(7;10)(q34;q24) |
TRB/TLX1 |
|
t(7;11)(q34;p15) |
TRB/LMO1 |
|
t(7;11)(q34;p13) |
TRB/LMO2 |
|
t(14q11.2;var) |
TRAD |
|
t(8;14)(q24.1;q11.2) |
MYC/TRAD |
|
t(10;14)(q24;q11.2) |
TLX1/TRAD |
|
t(11;14)(p15;q11.2) |
LMO1/TRAD |
|
t(11;14)(p13;q11.2) |
LMO2/TRAD |
|
del(17p) |
TP53 |
Reference Values
An interpretive report will be provided.
Interpretation
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.
Clinical Reference
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
Day(s) Performed
Monday through Friday
Report Available
7 to 10 daysTest Classification
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.CPT Code Information
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)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| COGTF | COG, ALL (T-cell), FISH | 101663-3 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 602286 | Result Summary | 50397-9 |
| 602287 | Interpretation | 69965-2 |
| 602288 | Result Table | 93356-4 |
| 602289 | Result | 62356-1 |
| GC016 | Reason for Referral | 42349-1 |
| GC017 | Specimen | 31208-2 |
| 602291 | Source | 31208-2 |
| 602292 | Method | 85069-3 |
| 602293 | Additional Information | 48767-8 |
| 602294 | Disclaimer | 62364-5 |
| 602295 | Released By | 18771-6 |
Forms
If not ordering electronically, complete, print, and send a Children's Oncology Group Test Request (T829) with the specimen.
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