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Genetic and epigenetic determinants mediate proneness of oncogene breakpoint sites for involvement in TCR translocations.
Larmonie, N S D; van der Spek, A; Bogers, A J J C; van Dongen, J J M; Langerak, A W.
Afiliación
  • Larmonie NS; Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • van der Spek A; Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Bogers AJ; Department of Cardio-thoracic Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • van Dongen JJ; Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Langerak AW; Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Genes Immun ; 15(2): 72-81, 2014 Mar.
Article en En | MEDLINE | ID: mdl-24304972
T-cell receptor (TCR) translocations are a genetic hallmark of T-cell acute lymphoblastic leukemia and lead to juxtaposition of oncogene and TCR loci. Oncogene loci become involved in translocations because they are accessible to the V(D)J recombination machinery. Such accessibility is predicted at cryptic recombination signal sequence (cRSS) sites ('Type 1') as well as other sites that are subject to DNA double-strand breaks (DSBs) ('Type 2') during early stages of thymocyte development. As chromatin accessibility markers have not been analyzed in the context of TCR-associated translocations, various genetic and epigenetic determinants of LMO2, TAL1 and TLX1 translocation breakpoint (BP) sites and BP cluster regions (BCRs) were examined in human thymocytes to establish DSB proneness and heterogeneity of BP site involvement in TCR translocations. Our data show that DSBs in BCRs are primarily induced in the presence of a genetic element of sequence vulnerability (cRSSs, transposable elements), whereas breaks at single BP sites lacking such elements are more likely induced by chance or perhaps because of patient-specific genetic vulnerability. Vulnerability to obtain DSBs is increased by features that determine chromatin organization, such as methylation status and nucleosome occupancy, although at different levels at different BP sites.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Proteínas Proto-Oncogénicas / Proteínas de Homeodominio / Proteínas Adaptadoras Transductoras de Señales / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico / Puntos de Rotura del Cromosoma / Proteínas con Dominio LIM Tipo de estudio: Prognostic_studies Límite: Child / Child, preschool / Humans / Infant / Newborn Idioma: En Revista: Genes Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / BIOLOGIA MOLECULAR Año: 2014 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Proteínas Proto-Oncogénicas / Proteínas de Homeodominio / Proteínas Adaptadoras Transductoras de Señales / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico / Puntos de Rotura del Cromosoma / Proteínas con Dominio LIM Tipo de estudio: Prognostic_studies Límite: Child / Child, preschool / Humans / Infant / Newborn Idioma: En Revista: Genes Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / BIOLOGIA MOLECULAR Año: 2014 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido