It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies.
Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment, and a multivariate model created from three gene-expression signatures predicted survival both in patients who received CHOP and patients who receive R-CHOP.
The dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, is described and the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MyD88 mutations are supported.
DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma and this gene-based predictor and the international prognostic index were independent prognostic indicators.
The criteria and significance of early or precursor lesions and the identification of certain lymphoid neoplasms largely associated with particular age groups, such as children and the elderly are addressed, and the issue of borderline categories having overlapping features with large B-cell lymphomas is reviewed.
The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease.