Applied molecular genetics in the diagnosis of malignant non-Hodgkin's lymphoma

Molecular DNA analysis has contributed to our understanding of lymphoproliferative disorders and aids the diagnosis of complicated lymphoma samples. The Southern blot procedure, still the gold standard for molecular genetic confirmation of clonality and lymphocyte lineage, is challenged by the simple and time-saving polymerase chain reaction (PCR) approach, which requires only small amounts of DNA and works for paraffin-embedded tissues. The effectiveness of PCR in rearrangement analyses of T-cell receptor gamma and immunoglobulin heavy chain genes is well documented. Though high sensitivity is achieved with the PCR-based detection of the t(14;18) translocation, more elaborate analyses of the other rearranging immune receptor genes and of translocations t(11;14) and t(8;14) require the Southern blot technique. Detection of bcl-2, bcl-1, and c-myc gene translocation goes beyond the assessment of clonality or lineage; these abnormalities may help to recognize the cellular compartment from which the tumor lymphocytes originate or, in the case of c-myc, may have prognostic impact. Molecular genetics bears the potential to identify new criteria for lymphoma diagnosis in conjunction with cytomorphology and immunophenotyping.