CHARACTERIZATION OF THE CHOP BREAKPOINTS AND FUSION TRANSCRIPTS IN MYXOID LIPOSARCOMAS WITH THE 12-16-TRANSLOCATION

Myxoid liposarcomas are cytogenetically characterized by t(12; 16)(q13 ;p11). The translocation results in rearrangements of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a fusion gene where the RNA -binding domain of FUS is replaced by the DNA-binding and leucine zipp er dimerization domain of CHOP, In the present study, we have mapped 1 6 genomic breakpoints in the region of the CHOP gene and isolated and sequenced a new variant (type II) of the chimeric PUS/CHOP transcript, The genomic breakpoints were dispersed along a 7.50-kilobase pair reg ion from a SstI cleavage site upstream of the promoter of CHOP to a Ps tI cleavage site within intron 1. Reverse transcriptase-polymerase cha in reaction analysis of tumor samples demonstrated the presence of two variant fragments, 654 base pairs (type I) and 378 base pairs (type I I) in size, Of the 13 samples analyzed, 7 showed the smaller, 3 showed the larger, and 3 showed both types of transcripts, We cloned and seq uenced the two fragments and found in type II a novel fusion point in the FUS mRNA 275 base pairs upstream of that present in the type I tra nscript, In both types of transcripts the interrupted FUS is followed by the entire exon 2 of CHOP, As a consequence the normally nontransla ted exon 2 is translated and in both types there is in the junction be tween FUS and CHOP a shift from a FUS glycine codon to a valine codon in the chimeric mRNA.