Genomic characterisation of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a genomically heterogenous disease comprised of many subtypes that display significantly different clinical outcomes, in the context of treatment with conventional immunochemotherapy. Poor clinical outcomes in some subtypes, and imperfect identification of high risk individuals in otherwise low risk subgroups, demonstrate there is room for improvement in the subclassification and risk stratification of DLBCL. In addition, more comprehensive profiling may lead to improved molecular testing guided treatment selection. Existing characterisation and risk stratification strategies, such as division of DLBCL into activated B-cell (ABC) and germinal centre B-cell (GCB) subtypes, although prognostically useful, may oversimplify the underlying biology and have proven to be less useful in improving therapy selection. Several groups have proposed more predictive molecular testing based prognostic models with potentially more relevance to therapy choice. These alternative approaches use more resource intensive comprehensive genomic profiling strategies which present practical challenges to implement in diagnostic laboratories. The addition of genomic testing to the subclassification of DLBCL shows promise, but laboratories must identify testing strategies relevant to clinical practice. A consensus on optimal molecular profiling techniques is yet to be achieved. In this article we review various next generation sequencing-based analytical techniques and molecular classification models proposed recently. Emerging therapeutics where molecular profiling may guide patient selection are also reviewed. The potential utility of genomic testing in DLBCL is discussed, in addition to practical considerations when considering introducing genomics into the diagnostic laboratory.