Recent advances in molecular pathology: A review. Some Aspects of Chromosome Changes in Cancer

Chromosomal changes, numerical and/or structural are usually present in malignant cells. As far aswe can tell, chromosomal changes may predispose to cancer. Certain structural changes and/or numerical abnormalities may herald the invasive stage of cancer, with marker chromosomes such as the Ph¹ and the long acrocentric chromosomes possibly being particularly significant in malignant transformation. Chromosomal studies also provide evidence for clonal evolution from a single stem cell in tumor formation. Evolution implies selection and Lejeune (1965) has proposed some laws which govern this process: (1) duplication of normal or abnormal supernumerary chromosomes; (2) mechanisms involving self-recognition which, in most instances, would protect against neoplasia, but occasionally may induce malignant transformation by causing chromosomal changes which either promote mutational events, potentiate oncogenic agents, and/or confer a selective growth advantage on the cell involved; and (3) initiation of the neoplastic process may be produced by specific marker chromosomes. These are only suggestions: there is as yet no proof that the common pathway of oncogenic agents are chromosomal aberrations. We need to extend the types of studies we have described, with particular emphasis on the early and preinvasive stages of cancer and clearer morphologic studies of marker chromosomes using thymidine-labeled tritiated chromosomes. In addition, such elegant techniques as developed by Beerman (1964) to study the control of differentiation at the chromosomal level, the beautiful electromicroscopic work of Brinkley (1969) showing the ultrastructural changes of damaged chromosomes, and the ingenious studies by Weiss and Green (1967) and others to investigate the properties of somatic hybrid cell lines and SV40-transformed human cells may become of considerable help in the pursuit of the relationship between chromosome changes and neoplasia. The latter technique may be particularly valuable in providing information about the location of specific genes in the human karyotype which we so badly need in order to obtain a fuller understanding of the relationship between genetic alterations and the properties of neoplastic cells (Littlefield, 1969).