Molecular genetic diagnosis of leukemias and lymphomas

Leukemias and lymphomas are genetically characterized by pathogenetically important, disease-specific mutations in the malignant cells. Many of the mutations arise through balanced chromosomal rearrangements, often translocations, that fuse oncogenes with other gene loci. In some instances, this leads to the formation of a qualitatively new hybrid gene encoding a leukemogenic or lymphomogenic protein product, whereas on other occasions the result is deregulation of an otherwise normal gene. The demonstration of such gene rearrangements is of both diagnostic and prognostic value and hence serves as an important supplement to the more traditional phenotype-based investigative techniques. All available methods to detect neoplasia-specific, acquired mutations have both advantages and disadvantages, depending partly on the level of resolution at which they operate (chromosomes, nucleic acids, proteins), but also on the specific characteristics of each individual technique. Ideally, the initial genetic diagnosis of a given tumor should be reached by means of an open-framed screening technique, whereas less labour-intensive, specific techniques may be used during the subsequent follow-up of the patient. The most reliable and complete information is always obtained by combining cytogenetic, molecular cytogenetic, and strictly molecular genetic investigations. However, such an approach may be too cumbersome and expensive to be taken routinely.