Chromosomal Instability in Tumor Initiation and Development

Abstract

Chromosomal instability (CIN) is one of the major forms of genomic instability in various human cancers and is recognized as a common hallmark of tumorigenesis and heterogeneity. However, some malignant tumors show a paucity of chromosomal alterations, suggesting that tumor progression and evolution can occur in the absence of CIN. It is unclear whether CIN is stable between precursor lesions, primary tumor, and metastases or if it evolves during these steps. In this review, we describe the influence of CIN on the various steps in tumor initiation and development. Given the recognized significant effects of CIN in cancer, CIN-targeted therapeutics could have a major impact on improving clinical outcomes.

Figure 1.

CIN in cancer. A, Paths to CIN. Mechanisms leading to defects in chromosome instability (see text for details). B, The critical role of CIN in the development of cancer. CIN is included in whole-chromosomal losses and gains (numerical CIN) and subchromosomal gains, losses, and translocations (structural CIN). Increasing CIN has been correlated with key tumor features through chromosomal alterations that can contribute to metastases (see text for details).