Chromosome instability and deregulated proliferation: an unavoidable duo.
The concept that aneuploidy is a characteristic of malignant cells has long been known; however, the idea that aneuploidy is an active contributor to tumorigenesis, as opposed to being an associated phenotype, is more recent in its evolution. At the same time, we are seeing the emergence of novel roles for tumor suppressor genes and oncogenes in genome stability. These include the adenomatous polyposis coli gene (APC), p53, the retinoblastoma susceptibility gene (RB1), and Ras. Originally, many of these genes were thought to be tumor suppressive or oncogenic solely because of their role in proliferative control. Because of the frequency with which they are disrupted in cancer, chromosome instability caused by their dysfunction may be more central to tumorigenesis than previously thought. Therefore, this review will highlight how the proper function of cell cycle regulatory genes contributes to the maintenance of genome stability, and how their mutation in cancer obligatorily connects proliferation and chromosome instability.
London Regional Cancer Program, University of Western Ontario, ON, Canada.
Courtney H
CH
Coschi
Frederick A
FA
Dick
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism; D000782:Aneuploidy; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D043171:Chromosomal Instability / Q000235:genetics*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D051381:Rats; D019572:Retinal Neoplasms / Q000235:genetics / Q000378:metabolism; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins