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Chromosome instability and deregulated proliferation: an unavoidable duo

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Abstract

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.

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Abbreviations

APC:

Adenomatous polyposis coli

CDK:

Cyclin dependent kinase

CIN:

Chromosome instability

DDR:

DNA damage response

LXCXE:

Leucine-any amino acid-cysteine-any amino acid-glutamate

MMTV:

Mouse mammary tumor virus promoter

OIS:

Oncogene induced senescence

PARP:

Poly ADP ribose polymerase

RB:

Retinoblastoma

S-CIN:

Segmental chromosome instability

W-CIN:

Whole chromosome instability

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Acknowledgments

C.H.C. is a recipient of a CIHR PhD studentship and is a member of the CaRTT training program. Research in F.A.D.’s laboratory is supported by grants from the Canadian Institutes for Health Research and the Canadian Cancer Society.

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  1. London Regional Cancer Program, University of Western Ontario, London, ON, Canada

    Courtney H. Coschi & Frederick A. Dick

  2. Children’s Health Research Institute, University of Western Ontario, London, ON, Canada

    Frederick A. Dick

  3. Department of Biochemistry, University of Western Ontario, London, ON, Canada

    Courtney H. Coschi & Frederick A. Dick

  4. Cancer Research Laboratories, 790 Commissioners Road East, London, ON, N6A 4L6, Canada

    Frederick A. Dick

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Coschi, C.H., Dick, F.A. Chromosome instability and deregulated proliferation: an unavoidable duo. Cell. Mol. Life Sci. 69, 2009–2024 (2012). https://doi.org/10.1007/s00018-011-0910-4

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