Abstract
The t(14;18)(q32;q21) involving the MALT1 and IGH genes is a recurrent abnormality in MALT lymphomas. So far, molecular genetic characterization of the t(14;18)/IGHMALT1 has only been performed in 2 cases and revealed a fusion of the entire coding region of MALT1 to the IGH locus.
We herein report the molecular genetic analyses of 2 new cases of MALT lymphoma harboring the t(14;18)/IGH-MALT1 using fluorescence in situ hybridization (FISH) and we determined the molecular characteristics at the IGH-MALT1 junctions using long-distance PCR (LD-PCR). The first case, a 71-year-old female, presented with an extranodal MALT lymphoma of the conjunctiva, stage IEA. The second case, a 53-year-old-male patient, was diagnosed as having a MALT lymphoma originating from the lung. FISH with PAC clones 117B5 and 59N7 revealed a translocation involving MALT1. Further FISH assays with probes hybridizing to MALT1 and IGH showed the t(14;18)(q32;q21)/IGH-MALT1. By FISH with specific probes for the P53, P16, RB1, and ATM genes no deletions of these genes were found. The IGH-MALT1 fusion was confirmed by LD-PCR on patients’ DNA with nested primers for the MALT1 and IGH genes. Cloning and sequencing of the purified PCR products revealed a fusion of sequences upstream of the coding region of MALT1 to the JH segment of the IGH locus in both cases. The breaks on chromosome 18 were located in the 5′ non-coding region of MALT1, only 13 nucleotides apart from each other. The breaks at IGH were located in the JH4 joining segment in both cases and showed features of a V(D)J-mediated recombination. Deletion and “de novo” nucleotides additions at the point of joining were observed in case 1. Furthermore, a detailed analysis of the “de novo” nucleotides additions in this case revealed the presence of DH segments of the DH gene D3-10 in the JH/MALT1 junction.
Our findings indicate that
the pathomechanism underlying the t(14;18)/IGH-MALT1 in MALT lymphomas is probably based on an illegitimate V(D)J recombination at IGH, similar to other IGH-associated translocations, such as the t(14;18)/IGH-BCL2 in follicular lymphomas and the t(11;14)/CCND1-IGH in mantle cell lymphomas and that the events leading to the t(14;18)/IGH-MALT1 might take place during an initial DH-to-JH or a later VH-to-DJH joining.