Test ID: COGBF    
B-Lymphoblastic Leukemia/Lymphoma, Children’s Oncology Group Enrollment Testing, FISH, Varies

Evaluation of pediatric bone marrow and peripheral blood specimens by FISH probe analysis for classic rearrangements and chromosomal copy number changes associated with B lymphoblastic leukemia/lymphoma and Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) in patients being considered for enrollment in Children's Oncology Group (COG) clinical trials and research protocols

As an adjunct to conventional chromosome studies in performed in pediatric patients with B-ALL and Ph-like ALL being considered for enrollment in COG protocols

Cytogenetic testing is important for the diagnostic and prognostic classification of pediatric neoplasia and it is a critical element for the enrollment of children into clinical trials affiliated with the Children’s Oncology Group (COG).

For over 25 years, the Mayo Clinic Genomics Laboratory has served as one of a select number of laboratories in the United States approved by the COG for the conventional chromosome analysis and FISH analysis of pediatric bone marrow, peripheral blood, and tissue specimens. All enrollment-required elements of cytogenetic testing will be electronically submitted by the Mayo Clinic Genomics Laboratory within the guidelines of COG.

This test detects neoplastic clones associated with common chromosome abnormalities in patients with B-Lymphoblastic Leukemia/Lymphoma (B-ALL). Identification of kinase-activating chromosome abnormalities in patients with Philadelphia chromosome-like B Lymphoblastic Leukemia/Lymphoma (Ph-like ALL) may be beneficial for therapeutic decision making.

This test is only performed on specimens from pediatric patients who are candidates for enrollment in Children's Oncology Group (COG) clinical trials and research protocols and may be ordered in 4 distinct ways allowing different combinations of probes to be utilized based on the clinical question:

-Standard (diagnostic) B-lymphoblastic leukemia/lymphoma (B-ALL) FISH panel

-Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel

-Combined-Standard (diagnostic) B-ALL FISH panel + Ph-like ALL panel

-Individual B-ALL FISH probes (per client request)

The specific B-ALL FISH panel or FISH probes requested must be noted on the request form or in the reason for referral. If no specific panel or FISH probe request is indicated, the "Standard (diagnostic) B-ALL FISH panel" will be performed.

The Standard (diagnostic) B-ALL FISH panel includes testing for the following abnormalities, using the FISH probes listed:

Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1

t(12;21)(p13;q22), ETV6/RUNX1 fusion, ETV6/RUNX1 D-FISH

iAMP21, RUNX1 amplification, ETV6/RUNX1 D-FISH

t(9;22)(q34;q11.2), BCR/ABL1 fusion, BCR/ABL1 D-FISH

t(1;19)(q23;p13), PBX1/TCF3 fusion, PBX1/TCF3 D-FISH

t(11q23;var), MLL (KMT2A) rearrangement, MLL (KMT2A) break-apart

del(9p), CDKN2A deletions, CDKN2A/D9Z1

t(14q32;var), IGH rearrangement, IGH break-apart

del(17p), TP53 deletions, TP53/D17Z1

8q24.1 rearrangement, MYC break-apart

t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement, P2RY8 break-apart

t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement, CRLF2 break-apart

-When an MLL (KMT2A) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(4;11)(q21;q23) AFF1/MLL, t(6;11)(q27;q23) MLLT4/MLL, t(9;11)(p22;q23) MLLT3/MLL, t(10;11)(p13;q23) MLLT10/MLL, t(11;19)(q23;p13.1) MLL/ELL, or t(11;19)(q23;p13.3) MLL/MLLT1.

-When an IGH and/or CRLF2 rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14) (p11.32;q32) cryptic translocation.

-When an extra signal of ABL1 is identified in BCR/ABL1 testing, reflex testing will be performed using the ABL1 break-apart probe set to identify the presence or absence of an ABL1 rearrangement.

-If a MYC rearrangement is identified, break-apart probe sets for BCL2 and BCL6 may be performed.

*The "Standard (diagnostic) B-ALL FISH panel" will be automatically reflexed to the Philadelphia Ph-like ALL panel on pediatric and young adult patients (age <30) who demonstrate normal or nonclassical abnormalities on the Standard (diagnostic) panel. In other circumstances, the Ph-like ALL panel may be recommended and the client notified before performing this testing.

The Ph-like ALL panel includes testing for the following kinase activating chromosome abnormalities, using the FISH probes listed below as well as IKZF1 deletion which often accompanies Ph-like ALL:

-t(1q25;var), ABL2 rearrangement, ABL2 break-apart

-t(5q33;var), PDGFRB rearrangement, PDGFRB break-apart

-t(9p24.1;var), JAK2 rearrangement, JAK2 break-apart

-t(9q34;var), ABL1 rearrangement, ABL1 break-apart

-t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement, P2RY8 break-apart

-t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement, CRLF2 break-apart

-When a PDGFRB rearrangement is identified, reflex testing will be performed using the PDGFRB/ETV6 fusion probe set to identify the potential t(5;12)(q33;p13) translocation.

-When a CRLF2 rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14) (p11.32;q32) "cryptic translocation."

This test includes a charge for application of the first probe set (2 FISH probes) and professional interpretation of results. Additional charges will be incurred for all reflex probes performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.

The following testing algorithm is recommended for patients with B-lymphoblastic leukemia/lymphoma (B-ALL):

-At diagnosis, standard (diagnostic) B-ALL FISH panel and/or conventional chromosome studies (COGBM / Chromosome Analysis, Hematologic Disorders, Children's Oncology Group Enrollment Testing, Bone Marrow) should be performed. If there is limited specimen available, only the COGBF / B-Lymphoblastic Leukemia/Lymphoma, Children's Oncology Group Enrollment Testing, FISH, Varies will be performed.

-For children in whom disease relapse or a secondary myeloid neoplasm is a concern and enrollment in a new COG protocol is being considered; COGBM for bone marrow chromosome analysis is appropriate.

-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 BALLF / B-Lymphoblastic Leukemia/Lymphoma, FISH, Varies.

Fluorescence In Situ Hybridization (FISH)