Clinical applications of molecular genetic testing in hematologic malignancies: Advantages and limitations

Abstract

Genetic abnormalities are the basis of cancer, and we now finally have a classification system of hematologic malignancies that acknowledges both the key role of genetics in the definition of specific entities, as well as in highlighting the prognostic heterogeneity of what were previously thought to be uniform diseases.1 The development of clinically useful molecular assays has been spawned largely by the dissection of rather specific translocations that essentially define distinct disease entities, and the exploitation of the physiologic process of antigen receptor gene rearrangements in lymphoid cells. Thus, by far most of these assays are directed at these pathologic and physiologic rearrangements, respectively. Other molecular phenomena, mostly unrelated to these 2 broad mechanisms, have also been identified, and which will soon likely also enter into the ever expanding armamentarium of molecular genetic assays, that help to refine diagnoses in a more biologically and clinically rational manner. The purpose of this report is not to provide an encyclopedic review of all the molecular targets available for study.2-4 Rather, the intent is to highlight some of those scenarios in which molecular genetic testing are of especial value (Table 1), and specifically where they provide important data that are not always evident from “routine” pathologic evaluation, such as morphology, histology, immunophenotyping, and karyotyping. The primary focus here is on phenomena other than antigen receptor gene rearrangements, which are detailed elsewhere in this issue.5 Additionally, the not insignificant pitfalls and caveats of such testing will also be briefly overviewed. ADVANTAGES OF MOLECULAR TESTING