Heterogeneity of the AP12-MALT1 gene rearrangement in MALT-type lymphoma

The translocation t(11;18)(q21;q21), which is the most frequent chromosomal aberration in extranodal marginal zone B cell lymphomas of MALT-type, was characterised in a series of 34 biopsies, including 18 gastric non-Hodgkin' s lymphomas (NHL) of MALT-type, six MALT-type NHL of extragastral origin an d 10 extranodal large B cell lymphomas (LBL). Based on fluorescence in situ hybridisation, STS-PCR analysis and screening of genomic PAC libraries, a physical map of contiguous DNA probes on chromosome 11 was constructed cont aining the anti-apoptotic genes API2 and API1 adjacent to the translocation breakpoint. RACE-PCR experiments revealed MALT1 the chromosome 18-derived fusion partner of API2, which has also been reported recently by other grou ps. RT-PCR analysis and DNA sequencing demonstrated the expression of an AP I2-MALT1 fusion transcript in 18/24 gastral and extragastral MALT-type lymp homas. In none of 10 LBLs was a translocation specific RT-PCR product detec ted. Five variants of the fusion transcript were identified and in all inst ances the open reading frame of the fused portion of the MALT1 gene was mai ntained. The molecular analysis of these variants allowed the design of opt imised assays for the diagnosis of the APM-MALT1 gene rearrangement.