We discuss the relatedness between the expression landscape and classifier signatures and their functional cell of origin background. This landscape is governed by the germinal center (GC) reaction and relates different subtypes to different states along the reaction path. Based on a whole transcriptome landscape of B-cell lymphoma, we show that one major caveat in the task of classification is represented by the rather fuzzy distribution of individual tumors without clear-cut borderlines between most of the subtypes, preventing their unambiguous association with clear-cut entities. Molecular classification schemes, first of all, derived from whole transcriptome gene expression data largely improved subtyping and functional understanding.
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They divide into a series of subtypes, such as Diffuse Large B-cell lymphomas (DLBCL), Burkitt Lymphomas (BL), Follicular lymphomas (FL), and further, into several subclasses and rarer subtypes of finer granularity, which makes them one of the most heterogeneous cancer entities. Germinal center-derived B-cell lymphomas constitute a very heterogeneous group of neoplasms with diverse clinical presentations, prognoses, and responses to therapy.
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