title: The molecular pathogenesis of B-cell non-Hodgkin lymphoma.
abstract: The B-cell non-Hodgkin lymphomas (B-NHL) are a diverse group of haematological malignancies which arise from the mature B-lymphocyte compartment. Recently, our understanding of the molecular pathogenesis of these disorders has greatly increased due to technological advances such as high-throughput DNA sequencing techniques. A paradigm of B-NHL pathogenesis has emerged where the normal genetic processes that are central to generating B-cell receptor diversity (somatic hypermutation and class switch/VDJ recombination) also drive the genesis of large-scale, chromosomal-level genetic lesions and smaller-scale gene-level mutations to produce the malignant phenotypes observed. Whilst a significant degree of genetic heterogeneity exists within each B-NHL subtype, the genetic lesions present within each subtype show a degree of convergence on common intracellular signalling, epigenetic and cell cycle pathways. This convergence gives an insight into the key oncogenic drivers of specific B-NHL subtypes and potential targets for therapeutic intervention. This review covers the current understanding of the causative genetic processes of B-NHL, the associated driving molecular lesions and the implications of these findings for the treatment of this group of disorders.
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
authors.forename: Piers A
authors.initials: PA
authors.lastname: Blombery
authors.affiliation: Victorian Cancer Cytogenetics Service, St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, Vic., Australia.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Wall
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D009154:Mutation; D009857:Oncogenes / Q000235:genetics
keywords: Non Hodgkin lymphoma; molecular; next generation sequencing