Your browser doesn't support javascript.
loading
Longitudinal copy number, whole exome and targeted deep sequencing of 'good risk' IGHV-mutated CLL patients with progressive disease.
Rose-Zerilli, M J J; Gibson, J; Wang, J; Tapper, W; Davis, Z; Parker, H; Larrayoz, M; McCarthy, H; Walewska, R; Forster, J; Gardiner, A; Steele, A J; Chelala, C; Ennis, S; Collins, A; Oakes, C C; Oscier, D G; Strefford, J C.
Afiliação
  • Rose-Zerilli MJ; Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Gibson J; Centre for Biological Sciences, Faculty of Natural and Environmental Studies, University of Southampton, Southampton, UK.
  • Wang J; Bioinformatics Unit, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Tapper W; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Davis Z; Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
  • Parker H; Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Larrayoz M; Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
  • McCarthy H; Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
  • Walewska R; Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
  • Forster J; Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Gardiner A; Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
  • Steele AJ; Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Chelala C; Bioinformatics Unit, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Ennis S; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Collins A; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Oakes CC; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, USA.
  • Oscier DG; Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Strefford JC; Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
Leukemia ; 30(6): 1301-10, 2016 06.
Article em En | MEDLINE | ID: mdl-26847028
The biological features of IGHV-M chronic lymphocytic leukemia responsible for disease progression are still poorly understood. We undertook a longitudinal study close to diagnosis, pre-treatment and post relapse in 13 patients presenting with cMBL or Stage A disease and good-risk biomarkers (IGHV-M genes, no del(17p) or del(11q) and low CD38 expression) who nevertheless developed progressive disease, of whom 10 have required therapy. Using cytogenetics, fluorescence in situ hybridisation, genome-wide DNA methylation and copy number analysis together with whole exome, targeted deep- and Sanger sequencing at diagnosis, we identified mutations in established chronic lymphocytic leukemia driver genes in nine patients (69%), non-coding mutations (PAX5 enhancer region) in three patients and genomic complexity in two patients. Branching evolutionary trajectories predominated (n=9/13), revealing intra-tumoural epi- and genetic heterogeneity and sub-clonal competition before therapy. Of the patients subsequently requiring treatment, two had sub-clonal TP53 mutations that would not be detected by standard methodologies, three qualified for the very-low-risk category defined by integrated mutational and cytogenetic analysis and yet had established or putative driver mutations and one patient developed progressive, therapy-refractory disease associated with the emergence of an IGHV-U clone. These data suggest that extended genomic and immunogenetic screening may have clinical utility in patients with apparent good-risk disease.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Cadeias Pesadas de Imunoglobulinas / Dosagem de Genes / Exoma / Mutação Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Humans / Middle aged Idioma: En Revista: Leukemia Assunto da revista: HEMATOLOGIA / NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Cadeias Pesadas de Imunoglobulinas / Dosagem de Genes / Exoma / Mutação Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Humans / Middle aged Idioma: En Revista: Leukemia Assunto da revista: HEMATOLOGIA / NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article