Primary chromosome abnormalities in human neoplasia

Abstract

At the cellular level, cancer is a genetic disease; genetic changes in somatic cells are essential events in neoplasia. In a majority of cases these changes involve large enough blocks of genetic material to be visible in the microscope. The chromosome aberrations in neoplastic disorders are probably of three kinds: (1) primary abnormalities, which are essential steps in establishing the tumor; (2) secondary abnormalities, which develop only after the tumor has developed, but which nevertheless may be important in tumor progression; and (3) cytogenetic noise, which is the background level of nonconsequential aberrations. These latter changes are, in contrast to the primary and secondary changes, randomly distributed throughout the genome. The primary abnormalities, of which several dozens have now been identified, are mostly strictly correlated with particular diseases and even with histopathological subtypes within a given disease. This has been evident in the leukemias for some years already, and information now accumulating on solid tumor karyology indicates a similar situation. Clonal chromosome abnormalities are a feature of both benign and malignant neoplasms, although the changes are often less massive in the former. Apart from being clinically useful as a diagnostic technique and an aid in prognostication, tumor cytogenetics also plays a role in identifying those genomic sites which harbor genes essential in the pathogenesis of neoplastic lesions. So far, two functionally different classes of directly cancer-relevant genes have been detected, the oncogenes and antioncogenes. There is every reason to believe that future investigations with cytogenetic and recombinant DNA methods will add to our knowledge of the biology of human neoplasia, in those tumor types where the characteristic genetic change is already partially known, and by identifying hitherto unknown karyotypic abnormalities.