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Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies

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...

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Autores principales: Berger, Manfred, Dirksen, Uta, Braeuninger, Andreas, Koehler, Gabriele, Juergens, Heribert, Krumbholz, Manuela, Metzler, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575406/
https://www.ncbi.nlm.nih.gov/pubmed/23441188
http://dx.doi.org/10.1371/journal.pone.0056408
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author Berger, Manfred
Dirksen, Uta
Braeuninger, Andreas
Koehler, Gabriele
Juergens, Heribert
Krumbholz, Manuela
Metzler, Markus
author_facet Berger, Manfred
Dirksen, Uta
Braeuninger, Andreas
Koehler, Gabriele
Juergens, Heribert
Krumbholz, Manuela
Metzler, Markus
author_sort Berger, Manfred
collection PubMed
description 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.
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spelling pubmed-35754062013-02-25 Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies Berger, Manfred Dirksen, Uta Braeuninger, Andreas Koehler, Gabriele Juergens, Heribert Krumbholz, Manuela Metzler, Markus PLoS One Research Article 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. Public Library of Science 2013-02-18 /pmc/articles/PMC3575406/ /pubmed/23441188 http://dx.doi.org/10.1371/journal.pone.0056408 Text en © 2013 Berger et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Berger, Manfred
Dirksen, Uta
Braeuninger, Andreas
Koehler, Gabriele
Juergens, Heribert
Krumbholz, Manuela
Metzler, Markus
Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies
title Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies
title_full Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies
title_fullStr Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies
title_full_unstemmed Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies
title_short Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies
title_sort genomic ews-fli1 fusion sequences in ewing sarcoma resemble breakpoint characteristics of immature lymphoid malignancies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575406/
https://www.ncbi.nlm.nih.gov/pubmed/23441188
http://dx.doi.org/10.1371/journal.pone.0056408
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