Singling Out Chromosome Gains in Tumor Evolution

Abstract

In this issue of Cancer Cell, Sheltzer et al. shed new light on Theodor Boveri's century-old hypothesis by demonstrating that aneuploidy characterized by single-chromosome gains acts to suppress tumorigenesis and that aneuploidy itself is a nidus for genomic instability.

Figure 1. Single Chromosome Gains Slow Neoplastic Growth But Set the Stage for Malignancy

Aneuploidy, an abnormal number of chromosomes, is a hallmark of human cancers and associated with poor clinical outcome. Sheltzer et al. show that single-chromosome gains (+1) are persistent inhibitors of neoplastic growth (a) even in the presence of strong drivers of uncontrolled growth. Chromosome gains are found to be a source of chromosomal instability, allowing rare cells after a long lag phase to fortuitously hit a jackpot (b) of “chromosome rearrangements” that unleashes uninhibited tumor cell growth resulting in malignancy.