Cytogenetic heterogeneity: its role in tumor evolution

There is ample evidence that cytogenetic heterogeneity characterizes human solid tumors, despite the opposing influences of clonal origin and selection for tumor-specific chromosome aberrations. Different chromosome patterns are found within individual tumors and among phenotypically similar tumors. Some tumor cell populations contain mixtures of diploid and cytogenetically aberrant cells; others display multiple aberrant clones. The extent and biological significance of chromosomal heterogeneity is contrasted between examples of leukemias and of selected solid tumors (mainly of breast and central nervous system origin). Increasing degrees of chromosomal aberration appear correlated with increasingly malignant biological properties of tumors. Genic and chromosomal instability are potential sources for genetic diversity within all tumors. However, variations in local selective forces and differential survival within an expanding solid lesion may contribute to maintenance of a mixed cell population within the primary tumor. In turn, the resulting heterogeneity may permit selection and increase of aberrant cells that are responsible for tumor progression and metastasis.