Recent advances in the molecular characterization of human sarcomas have identified tumor-specific chromosomal translocations in many mesenchymal neoplasms. These genetic rearrangements frequently involve genes which encode transcriptional regulatory factors that play a pivotal role in tumorigenesis. Our laboratory is studying sarcoma-specific translocations involving zinc finger transcription factors with a particular focus on desmoplastic small round cell tumor (DSRCT), a primitive sarcoma with a t(11;22) involving the WT1 zinc finger transcription factor. We have identified a DSRCT with a unique breakpoint site that is characterized by insertion of a 468 bp LINE-1 element. LINE-1 elements are retrotransposons that can integrate into random genomic sites and may underlie some genetic disorders as the result of inactivating structural genes. These movable genetic elements have never previously been identified at the fusion site of a tumor-associated chromosomal translocation. Further analysis of other DSRCT breakpoint regions is indicated to determine the prevalence of LINE-1 insertion but this observation establishes a novel mechanism for juxtaposition of these genes in neoplastic cells.
