API2/MALT1 t(11;18) by FISH

F API MALT


Test Synonym:
Mucosa associated lymphoid tissue translocation gene 1


Asscociations:
MALT lymphoma



CPT Code:
88367x2 - Morphometric analysis, in situ hybridization, automated
88368 x2 - Morphometric analysis, in situ hybridization, manual


Turnaround Time:
3 days



Methodology:
Fluorescence in situ hybridization (FISH)



Specimen Requirements:

• 2.0 ml (min. 1.0 ml) peripheral blood in sodium heparin, EDTA accepted
• 1.0 ml (min. 0.5 ml) bone marrow in sodium heparin, EDTA accepted
• 5 mm3 fresh tissue in MPLN RPMI media
• 3.0 ml (min. 2.0ml) FNA in MPLN RPMI media
• 10% neutral buffered formalin fixed paraffin embedded tissue


Causes for Rejection:

Clotted specimen; Specimen exposed to extreme temperature; Anticoagulant toxic to cells; Insufficient number of cells; Improper fixative



Specimen Stability:

• Peripheral blood and bone marrow stable at 18-25°C for 72 hours
• Fresh tissue or FNA stable at 2-8°C for 72 hours


Storage and Handling:
• Whole blood and bone marrow ship ambient
• Fresh tissue, FNA or paraffin embedded tissue ship in a Styrofoam container with an ice pack (do not allow ice pack to directly contact sample)


Reference Range:
FISH results indicate whether rearrangement is present or absent.

In a normal cell without the t(11;18), two orange and two green signals will be detected indicating the presence of two intact copies of chromosome 11 and two intact copies of chromosome 18.

In a cell with a translocation involving 11q21 and 18q21, two fusion signals representing the two rearranged chromosomes will be identified.  One orange signal and one green signal will also be seen designating the normal chromosomes 11 and 18.

Indication:
MALT lymphomas (also known as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue) constitute about 8% of all non-Hodgkin lymphomas. The most common structural abnormality associated with MALT lymphomas is the translocation between 18q21 and 11q21. This rearrangement leads to the fusion of the apoptosis inhibitor-2 (API2) gene and MALT lymphoma-associated translocation (MALT1) gene. In general MALT lymphomas are low-grade lymphomas regardless of the fact that there is often dissemination to other mucosal sites, bone marrow, or multiple lymph nodes. Rare cases show histological transformation to aggressive diffuse large-dell lymphoma

The translocation between 11q21 and 18q21 juxtaposes the 5’API2 gene to the 3’MLT1 gene to for a fusion gene that encodes an abnormal but functioning chimeric protein.


The ALI2/MALT 1 probe assay can be performed on interphase or metaphase cells.


References:

  1. Mathijs B, Marynen P . (2001) t(11;18)(q21;q21). Atlas Genet Cytogenet Oncol Haematol. September.
  2. Bertoni F et al. (2006). Delving deeper into MALT lymphoma biology. J Clin Invest 116(1):22
  3. Cavalli F et al. (2001). MALT lymphomas. Hematology 2001(1):241
  4. Streubel B, et al. (2003). t(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood 101(6):2335