A novel FUS/CHOP chimera in myxoid liposarcoma

The cytogenetic hallmark of myxoid liposarcoma is the chromosomal aberratio n t(12;16)(q13;p11), which is pathognomonic for this tumor type. The transl ocation results in the hybrid gene FUS/CHOP, where the central and C-termin al parts of FUS, coding for the RNA binding domain and the RGG triplet moti f, are replaced by the full length CHOP protein. Thus, CHOP is under the co ntrol of the FUS promoter and the FUS/CHOP chimera contains the 5'-terminal part of FUS which provides a transcriptional activation function. Although different structural variations of the FUS/CHOP chimeric transcript have b een reported, none of them contains the parts of FUS encoding the RNA bindi ng properties. An explanation is the location of the genomic breakpoint in FUS, which frequently occurs in the region spanning exon 5 to intron 8. We describe here a case of myxoid liposarcoma containing two novel FUS/CHOP ch imeric transcripts and with the breakpoint occurring in intron 14 of FUS. R everse transcription-polymerase chain reaction, using FUS forward and CHOP reverse primers, amplified strongly a 2.1-kbp DNA fragment and weakly a 0.9 -kbp DNA fragment. Direct sequencing showed that in the 2.1-kbp transcript nt 1474, which corresponds to the third nucleotide of exon 14 of FUS, was i n-frame fused to exon 2 of CHOP. In the 0.9-kbp DNA fragment, exon 3 of FUS was in-frame fused to exon 2 of CHOP Genomic analyses revealed that the br eaks were located at the end of exon 14/beginning of intron 14 of FUS and i n intron 1 of CHOP and that microdeletions had occurred in the close vicini ty of the breakpoints. (C) 2000 Academic Press.