Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis

Abstract

Preface The mitotic checkpoint guards against chromosome missegregation and the production of aneuploid daughter cells. Aneuploidy is a common characteristic of tumor cells and has been proposed for over a century to drive tumor progression. However, recent evidence has revealed that although aneuploidy can increase the potential for cellular transformation, it also acts to antagonize tumorigenesis in certain genetic contexts. A clearer understanding of the tumor suppressive function of aneuploidy may reveal new avenues for anticancer therapy.

Caspase-2 deficiency promotes aberrant DNA-damage response and genetic instability

“…[24][25][26] GIN and CIN commonly arise from changes in whole chromosome number (aneuploidy) and there is strong evidence that aneuploidy is important for tumour development. 27 GIN precedes cellular transformation and oncogenesis and is frequently associated with loss of p53 function. 28,29 The activation of the DDR is therefore critical to maintain genome stability, but the mechanisms underlying the decision to activate DNA repair and survive or to die are not fully understood.…”

Loss of LIN9, a member of the DREAM complex, cooperates with SV40 large T antigen to induce genomic instability and anchorage-independent growth

“…Precise regulation of mitosis is important to prevent aneuploidy, a hallmark of most cancers (Holland and Cleveland, 2009). Aneuploidy can be caused by errors in mitosis and cytokinesis.…”

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

“…However, the SAC is not the only safety mechanism that should be considered when designing anti-cancer drugs targeting mitosis and cytokinesis of cancer cells. Evasion of the SAC can even be a driving force for chromosomal abnormalities [2,3,9]. Therefore, researchers have been studying other mechanisms that play a role in mitosis.…”

“…Therefore, Hanahan and Weinberg (2011) included genomic instability as an enabling characteristic in their updated Hallmarks of Cancer review [1]. Current evidence strongly suggests that chromosomal alterations are not only a feature of cancer cells but are also part of the driving force during malignant cellular transformation [2,3]. Significantly, errors in mitosis are prone to result in abnormal chromosome composition.…”