In their recent paper, Valind et al. test the theory that “aneuploidy automatically” destabilizes the karyotype (1). According to this theory, aneuploidy, an abnormal balance of chromosomes, destabilizes the karyotype automatically by unbalancing the cooperations of thousands of genes, especially mitosis genes: The more aneuploid the cell the more unstable is the karyotype (2–5). To test this theory, Valind et al.(1) compare chromosomal instabilities of normal diploid cells, cells from congenital near-diploid aneuploidies and from rare-balanced triploids, and cells from highly aneuploid, clonal cancers. Chromosomal instability is measured as the percentage of cells with abnormal chromosome copy numbers, defined as the aneusomy index (AI). Valind et al.’s (1) results show that the chromosomal instability indices of normal human cells are between 0.09 and 0.18 AI, those of congenital near-diploid aneuplodies—like Down, Patau, Edward, and other syndromes—range from 0.2 to 0.7 AI, and those of neardiploid to highly aneuploid, near-triploid colon cancers range from 1.2 to 4.7 AI. Accordingly, the authors conclude that congenital “aneuploidy was... insufficient to generate... cancer-like chromosomal instability”(1). It would seem, therefore, that the new data of Valind et al. support the concept that chromosomal instability is directly proportional to the degree of aneuploidy.

As an argument against the theory that aneuploidy destabilizes the karyotype automatically or “per se,” Valind et al.(1) cite the relatively low chromosomal instability of 0.66–1.8 AI of two congenital, chromosomally balanced triploidies, compared with the very high chromosomal instability of 4.8 AI of the chromosomally highly unbalanced near-triploid colon carcinoma SW480.