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Oncogenic events rather than antigen selection pressure may be the main driving forces for relapse in diffuse large B-cell lymphomas.
Rizzo, David; Viailly, Pierre-Julien; Mareschal, Sylvain; Bohers, Elodie; Picquenot, Jean-Michel; Penther, Dominique; Dubois, Sydney; Marchand, Vinciane; Bertrand, Philippe; Maingonnat, Catherine; Etancelin, Pascaline; Feuillard, Jean; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice; Ruminy, Philippe.
Afiliação
  • Rizzo D; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Viailly PJ; Department of biological hematology, Centre Hospitalier Universitaire Dupuytren, Limoges, France.
  • Mareschal S; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Bohers E; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Picquenot JM; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Penther D; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Dubois S; Department of pathology, Centre Henri Becquerel, Rouen, France.
  • Marchand V; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Bertrand P; Department of oncology genetics, Centre Henri Becquerel, Rouen, France.
  • Maingonnat C; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Etancelin P; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Feuillard J; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Bastard C; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Tilly H; INSERM U918, Centre Henri Becquerel, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
  • Jardin F; Department of oncology genetics, Centre Henri Becquerel, Rouen, France.
  • Ruminy P; Department of biological hematology, Centre Hospitalier Universitaire Dupuytren, Limoges, France.
Am J Hematol ; 92(1): 68-76, 2017 Jan.
Article em En | MEDLINE | ID: mdl-27737507
Little is known on the phylogenetic relationship between diagnostic and relapse clones of diffuse large B-cell lymphoma (DLBCL). We applied high throughput sequencing (HTS) of the VDJ locus of Immunoglobulin heavy chain (IGHV) on 14 DLBCL patients with serial samples, including tumor biopsies and/or peripheral blood mononuclear cells (PBMC). Phylogenetic data were consolidated with targeted sequencing and cytogenetics. Phylogeny clearly showed that DLBCL relapse could occur according either an early or a late divergent mode. These two modes of divergence were independent from the elapsed time between diagnosis and relapse. We found no significant features for antigen selection pressure in complementary determining region both at diagnosis and relapse for 9/12 pairs and a conserved negative selection pressure for the three remaining cases. Targeted HTS and conventional cytogenetics revealed a branched vs. linear evolution for 5/5 IGHV early divergent cases, but unexpected such "oncogenetic" branched evolution could be found in at least 2/7 IGHV late divergent cases. Thus, if BCR signaling is mandatory for DLBCL emergence, oncogenetic events under chemotherapy selection pressure may be the main driving forces at relapse. Finally, circulating subclones with divergent IGHV somatic hypermutations patterns from initial biopsy could be detected in PBMC at diagnosis for 4/6 patients and, for two of them, at least one was similar to the ones found at relapse. This study highlights that oncogenetic intraclonal diversity of DLBCL should be evaluated beyond the scope a single biopsy and represents a rationale for future investigations using peripheral blood for lymphoid malignancies genotyping. Am. J. Hematol. 92:68-76, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfoma Difuso de Grandes Células B / Cadeias Pesadas de Imunoglobulinas / Evolução Clonal / Recombinação V(D)J / Recidiva Local de Neoplasia Tipo de estudo: Observational_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfoma Difuso de Grandes Células B / Cadeias Pesadas de Imunoglobulinas / Evolução Clonal / Recombinação V(D)J / Recidiva Local de Neoplasia Tipo de estudo: Observational_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article