The aneuploidy paradox in cell growth and tumorigenesis

Abstract

Aneuploidy, an abnormal chromosome number, is a frequent characteristic of malignant cells, leading to the suggestion that aneuploidy drives tumorigenesis. In a recent issue of Science, Williams et al. identified a paradoxical relationship between aneuploidy and its linkage to tumorigenesis: chromosome gains in nontransformed cells are antiproliferative, despite frequently occurring in human tumors.

Figure 1. Chromosome gains commonly occur in human tumors, but cause proliferative defects in primary cells

A. Chromosome gains are the most common type of aneuploidy found in human tumors. The number of chromosomes per cell in carcinomas (top), hematopoietic cancers (middle) and sarcomas (bottom) are shown. Chromosome numbers were obtained from the Mitelman database of cancer chromosomes (Mitelman et al., 2006). B. Different types of aneuploidy have distinct effects on cell growth and tumorigenesis. Cells that have (left) lost chromosomes or (middle) exhibit continuing Chromosomal INstability (CIN) do not have a growth defect. (Right) Chromosome gains cause a proliferative disadvantage in primary cells, probably from increased levels of expression of the many genes encoded by the additional chromosome. Spontaneous immortalization can be accompanied by tetraploidization, which is probably the result of cytokinesis failure, as observed by Williams et al. However, tetraploidization is not a requirement for immortalization, as p19ARF^−/− MEFs are immortal and contain a near-diploid karyotype (Weaver and Cleveland, unpublished).