Response: The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas is a CpG-type translocation, but the t(11;18)(q21;q21)/API2-MALT1 translocation in MALT lymphomas is not

We thank Drs Tsai, Lu, and Lieber for their interest in our paper¹  and for this excellent response to our work regarding the molecular characteristics of MALT1 breakpoints in t(14,18)(q32;q21)/IGH-MALT1–positive MALT lymphomas. The authors added important information by showing a nonrandom accumulation of breakpoints around the dinucleotide sequence CpG in the MALT1 major breakpoint region (MALT1-MBR). Based on these findings they proposed that the IGH-MALT1 translocation belongs to a recently described group of CpG-Type translocations comprising the CCND1-IGH, the IGH-BCL2, and the PBX1-E2A translocations.² 

In a recent paper, the authors have shown that CpG-type translocations occur only in the pro-B/pre-B cell stage.²  These new findings strengthen our hypothesis that the mechanisms for the generation of breakpoints of IGH-associated translocations in MALT lymphomas, follicular lymphomas and mantle cell lymphomas are common and provide important information about the lymphomagenesis of t(14;18)/IGH-MALT1–positive MALT lymphomas.

The MALT1 gene is rearranged in a second chromosomal translocation, the t(11;18)(q21;q21)/API2-MALT1,³  which, as the authors illustrate, differs substantially from the IGH-MALT1 translocation concerning the proximity of MALT1 breakpoints to CpG regions. In the API2-MALT1 translocation, the breakpoints are distributed in a wide chromosomal region without CpG hotspots. The API2-MALT1 translocation is therefore not a CpG-Type translocation and may be associated with a different stage of B-cell development than the IGH-MALT1 translocation.

In this respect it is interesting to note, that the IGH-MALT1 translocation is mainly present in salivary gland, ocular, and cutaneous MALT lymphomas and often occurs in a context of an autoimmune disorder. The API2-MALT1 translocation characterizes up to 50% of gastrointestinal MALT lymphomas that develop generally in a background of a chronic Helicobacter pylori gastritis. In addition, the API2-MALT1 translocation is seen mostly as a sole chromosomal abnormality, whereas the IGH-MALT1 translocation is not seldomly accompanied by additional chromosomal abnormalities.