Characteristic sequence motifs located at the genomic breakpoints of the translocation t(12;16) and t(12;22) in myxoid liposarcoma

SummaryAimsTo analyse the characteristic sequence motifs around genomic breakpoints of translocations, t(12;16) and t(12;22), and to study the mechanisms underlying these chromosomal translocations in myxoid liposarcomas(MLS).MethodsGenomic DNA sequences derived from t(12;16) and t(12;22) were amplified by long-distance polymerase chain reaction (PCR) in six cases of MLS, and the DNA sequences around the breakpoints were analysed.ResultsGenomic sequences of the FUS-CHOP or EWSCHOP fusion gene were amplified in five and one MLS, respectively. Our sequence analysis revealed that the gene fusions were generated between intron 1 of the CHOP and either intron 5 (type II) or 7 (type I), or 8 (type III) of the FUS, or intron 7 of the EWS. The breakpoints in intron 1 of the CHOP were located near or within Alu repetitive sequences in the six cases. Sequences homologous to consensus recognition motifs of Translin were present adjacent to the breakpoints in the FUS, EWS, and CHOP genes. Sequences homologous to the topoisomerase II consensus site and palindromic oligomer sequences were also frequently found around the breakpoints in these genes. Moreover, Chi or Chilike sequences were found in three cases, alternating purinepyrimidine tracts and polyadenine/polythymine sequences were each found in one case.ConclusionsOur results suggest that characteristic sequence motifs located at the FUS, EWS and CHOP breakpoint regions, including Alu and palindromic oligomer sequences, are involved in the mechanism creating chromosomal translocations in MLS.