LINE-I ELEMENT INSERTION AT THE T(11-22) TRANSLOCATION BREAKPOINT OF A DESMOPLASTIC SMALL ROUND CELL TUMOR

A t(11;22)(p13;p12) chromosomal translocation, juxtaposing the Wilms' tumor (WT1) and Ewing's sarcoma (EWS) genes, is the cytogenetic hallma rk of desmoplastic small round cell tumor (DSRCT), a primitive multiph enotypic sarcoma arising in serosal tissues. Chimeric transcripts gene rated by this rearrangement encode an aberrant transcription factor th at fuses the 5' region of EWS with a 3' WT1 segment. We describe the i nsertion of a LINE-1 DNA mobile genetic element at the genomic breakpo int of a DSRCT chromosomal translocation. A 480 bp heterologous DNA se gment with homology to the LINE-1 DNA consensus sequence was located b etween EWS intron 8 and WT1 exon 8 in the productively rearranged alle le. Sequence homology corresponded to the LINE-1 ORF-2, which encodes a protein with reverse-transcriptase activity. The heterologous insert ed fragment was not evident in the germline of normal tissue from the patient, suggesting that transposition occurred in somatic cells, poss ibly during the process of chromosomal rearrangement. This case repres ents the first example of LINE-1 DNA transposition at the fusion site of a tumor-associated chromosomal rearrangement. (C) 1997 Wiley-Liss, Inc.