title: Genomic EWS-FLI1 fusion sequences in Ewing sarcoma resemble breakpoint characteristics of immature lymphoid malignancies.
abstract: Chromosomal translocations between the EWS gene and members of the ETS gene family are characteristic molecular features of the Ewing sarcoma. The most common translocation t(11;22)(q24;q12) fuses the EWS gene to FLI1, and is present in 85-90% of Ewing sarcomas. In the present study, a specifically designed multiplex long-range PCR assay was applied to amplify genomic EWS-FLI1 fusion sites from as little as 100 ng template DNA. Characterization of the EWS-FLI1 fusion sites of 42 pediatric and young adult Ewing sarcoma patients and seven cell lines revealed a clustering in the 5' region of the EWS-breakpoint cluster region (BCR), in contrast to random distribution of breakpoints in the FLI1-BCR. No association of breakpoints with various recombination-inducing sequence motifs was identified. The occurrence of small deletions and duplications at the genomic junction is characteristic of involvement of the non-homologous end-joining (NHEJ) repair system, similar to findings at chromosomal breakpoints in pediatric leukemia and lymphoma.
authors: University Hospital Erlangen, Department of Pediatrics, Erlangen, Germany.
authors: Manfred
authors: M
authors: Berger
authors: Uta
authors: U
authors: Dirksen
authors: Andreas
authors: A
authors: Braeuninger
authors: Gabriele
authors: G
authors: Koehler
authors: Heribert
authors: H
authors: Juergens
authors: Manuela
authors: M
authors: Krumbholz
authors: Markus
authors: M
authors: Metzler
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D005260:Female; D023061:Gene Order; D006801:Humans; D007945:Leukemia, Lymphoid / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics*; D051789:Proto-Oncogene Protein c-fli-1 / Q000737:chemistry / Q000235:genetics*; D034802:RNA-Binding Protein EWS / Q000737:chemistry / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS