Chromosomal Instability in Health and Disease

Dear Colleagues,

Chromosomal instability (CIN) and its consequence, aneuploidy, are predominant features of cancers. CIN results in structural and numerical chromosomal aberrations and leads to heterogeneity of such aberrations inside the same tumor. In conjunction with other forms of genomic and epigenomic instability, CIN underpins the most menacing aspect of cancer cells: their ability to evolve. This enables cancer cells to evade immunological surveillance, metastasize, and develop resistance to therapeutic drugs. Concurrently, CIN also introduces vulnerabilities in cancer cells, presenting potential avenues for anticancer therapies.

But is CIN exclusive to pathological processes? Even conservative estimates suggest that at least 5% of human somatic cells are aneuploid for one or more chromosomes, hinting at a consistent presence of CIN throughout ontogenesis. Cellular senescence, seemingly mediated by CIN and aneuploidy, may play a role in aging. However, the contribution of CIN and somatic aneuploidy to both normal and pathological aging remains a contentious topic.

On a population level, CIN may serve as a natural biological mechanism promoting the genomic variability of unicellular and multicellular organisms. This variability permits adaptive responses to environmental changes and, ultimately, drives the evolutionary process. Variations in chromosomal number and structure, such as translocations, deletions, duplications, inversions, and complex chromosomal rearrangements, have shaped the phylogenesis of many evolutionary lineages. Furthermore, during early embryonic development, CIN might act as a major factor in negative selection, ensuring the survival of embryos exhibiting robust genome integrity.

We invite researchers to contribute manuscripts related to these themes.

Dr. Anna V. Roschke
Guest Editor

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• chromosomal instability
• aneuploidy
• polyploidy
• cancer evolution
• chromosomal instability and aneuploidy in embryonic development
• chromosomal instability and polyploidy in evolutionary process
• somatic aneuploidy in senescence and ageing