The role of molecular genetics in medical oncology

Abstract

Molecular genetics is a powerful new tool for detection, diagnosis, evaluation of treatment, and understanding of the biology of malignant disease. The first malignant disease to be characterized by a specific cytogenetic aneuploid abnormality was chronic myelogenous leukemia (CML) which was first recognized in 1962 as an abnormal shortening of the long arm of either chromosome 21 or 22, the smallest chromosomes in the human genome. This cytogenetic abnormality was subsequently shown to represent not a loss of genetic material, but a pseudodiploid aneuploidy with a reciprocal translocation of chromosomal material from the long arms of chromosome 9 and 22. The discovery that the abl oncogene was located at the breakpoint on chromosome 9 allowed the molecular geneticists to identify the genetic material adjacent to the translocated material from chromosome 9 and because the breakpoint on chromosome 22 was variable but restricted to a small region, it was named the breakpoint cluster region (BCR). The BCR/abl gene has been found exclusively in leukemic cells from patients with CML. The somatic cells of the host are not involved and at least to date, every individual that has been found to have this gene has also had the disease CML. Approximately 15 % of CML patients lack the Philadelphia chromosome on cytogenetics. However, approximately half of these patients can be shown to have the BCR/abl neogene present as a masked translocation.