Chromosomal instability in development and disease: Beyond cancer evolution

Abstract

Chromosomal instability (CIN), an increased rate of changes in chromosome structure and number, has been classically associated with human disease as a way of evolving the cancer genome. In recent years, three additional research lines concerning the impact of CIN on human disease have been consolidated. First, beyond the generation of genomic copy number heterogeneity, CIN acts as a source of tumor growth, metastasis, and malignancy through additional mechanisms. Second, CIN is pervasive in early human development, and the resulting aneuploid cells are selectively removed from the fetus to give rise to healthy births. Third, CIN is associated with mosaic variegated aneuploidy, a rare familial disease that compromises brain development and contributes to tumor formation. Here, I will review recent advances in these three topics, with a particular focus on the use of model systems and organisms to understand the increasing impact of CIN on human biology and disease.