title: LINE-I element insertion at the t(11;22) translocation breakpoint of a desmoplastic small round cell tumor.
abstract: A t(11;22)(p13;p12) chromosomal translocation, juxtaposing the Wilms' tumor (WT1) and Ewing's sarcoma (EWS) genes, is the cytogenetic hallmark of desmoplastic small round cell tumor (DSRCT), a primitive multiphenotypic sarcoma arising in serosal tissues. Chimeric transcripts generated by this rearrangement encode an aberrant transcription factor that fuses the 5' region of EWS with a 3' WT1 segment. We describe the insertion of a LINE-I DNA mobile genetic element at the genomic breakpoint of a DSRCT chromosomal translocation. A 480 bp heterologous DNA segment with homology to the LINE-I DNA consensus sequence was located between EWS intron 8 and WT1 exon 8 in the productively rearranged allele. Sequence homology corresponded to the LINE-I ORF-2, which encodes a protein with reverse-transcriptase activity. The heterologous inserted fragment was not evident in the germline of normal tissue from the patient, suggesting that transposition occurred in somatic cells, possibly during the process of chromosomal rearrangement. This case represents the first example of LINE-I DNA transposition at the fusion site of a tumor-associated chromosomal rearrangement.
authors.affiliation: NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: M M
authors.initials: MM
authors.lastname: Nau
authors.forename: J
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: J I
authors.initials: JI
authors.lastname: Powell
authors.forename: C J
authors.initials: CJ
authors.lastname: Allegra
authors.forename: J J
authors.initials: JJ
authors.lastname: Wright
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004251:DNA Transposable Elements; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D016162:Genes, Wilms Tumor / Q000235:genetics*; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D034802:RNA-Binding Protein EWS; D012194:RNA-Directed DNA Polymerase; D018626:Retroelements; D012261:Ribonucleoproteins / Q000235:genetics*; D018228:Sarcoma, Small Cell / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: D004251:DNA Transposable Elements; D004273:DNA, Neoplasm; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D034802:RNA-Binding Protein EWS; D018626:Retroelements; D012261:Ribonucleoproteins; D012194:RNA-Directed DNA Polymerase