Molecular structure of the t(11;18). The genomic structure of the t(11;18) is shown in (A). In the center the MLT gene is shown as the darkly shaded area on the normal 18q; API2 andMMP20 are shown, respectively, as an open rectangle and a light gray rectangle on the normal 11q (not drawn to scale). Below each gene the PAC isolated for this gene is shown. For PAC 152M5 the position of the different BamHI fragments used for FISH experiments are indicated. On top the rearrangement in case 1 is illustrated: the der(11) fuses the 5′ end of API2 to the 3′ end of MLT,while on the der(18), as a result from the cryptic deletion of chromosome 11, the 5′ end of MLT is fused to the 5′ end ofMMP20. The transcriptional orientation of each gene is indicated by an arrow below each chromosome, showing that on the der(18) MLT and MMP20 do have an opposite transcriptional orientation. The genomic fusion fragments that were cloned from, respectively, the der(11) and the der(18) are indicated by the double lines. Below, the rearrangement of case 2 is shown: the der(11) fuses 5′ API2 to 3′ MLT. The breakpoint in API2 is identical to the one in case 1; the breakpoint in MLT occurred upstream of the breakpoint in case 1 (see 2B). FISH experiments suggest that the der(18) is the balanced reciprocal of the der(11). The localization of all breakpoints is indicated on the normal chromosomes by open triangles. (B) The structure of the different fusion cDNAs. On top the structure of API2 is shown with three aminoterminal BIR domains separated from the carboxyterminal RING domain by a CARD domain. TheAPI2 cDNA is truncated after the third BIR domain and fused in frame to MLT. As a result of the heterogeneity of the genomic breakpoints in case 2, 582 additional nucleotides, encoding two Ig-like C2 domains of MLT, are present in this fusion. An Ig gamma VDJ4-like sequence in MLT is shown by a cross-hatched box. The sequence and the translation of the different junction fragments is shown underneath each cDNA.