Practical role of molecular diagnostics in non-Hodgkin's lymphomas

Molecular techniques are becoming increasingly important in the analysis of NHL, both for diagnostic purposes and in order to evaluate prognosis accurately. The increasing number of techniques available renders evaluation of their relative roles important and a review of their informativity in NHL at diagnosis timely. Molecular equivalents of chromosomal translocations generate either a qualitative change due to the expression of a chimaeric, relatively tumour specific, protein, such as the NPM-ALK associated with the t(2;5) in ALCL or a quantitative change in the extent, stage or site of expression of a full length protein, due to its juxtapositioning to and deregulation by an Ig or TCR gene. The latter represents errors of the somatic recombination process which lymphoid precursors undergo. In NHL, this category includes BCL1/CCND1, BCL2, BCL6 and MYC. The molecular characteristics, the functional consequences and the main clinical correlations of each of these abnormalities is reviewed. At diagnosis, immunological detection of the deregulated 'protooncogene' may well provide the simplest, most appropriate screening technique for CCND1 and NPM-ALK induced ALK expression. BCL6 abnormalities demonstrate similarities to BCL2 and MYC and a combination of immunophenotypic, FISH, Southern blot and PCR techniques are useful in their characterization. For the approximately 50% of NHL without one of the above markers, identification of a clonal Ig or TCR rearrangement can provide a useful 'pan' B or T molecular equivalent, provided that the limitations of the detection techniques are appreciated. Appropriate use of these techniques will transform our ability to classify, stratify and eventually treat in a risk adapted manner, patients with NHL.