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A four-lane highway to cancer

Nature Reviews Molecular Cell Biology volume 17, page 398 (2016)Cite this article

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Aneuploidy — a cellular state characterized by the gain or loss of entire chromosomes or large chromosomal fragments — is commonly found in biopsies from a wide range of solid tumours. Moreover, the degree of aneuploidy in malignant cells is linked to key clinicopathological features, including genomic instability, propensity to metastatic dissemination and patient survival (Ganem et al.). During the past decade, several laboratories worldwide — including ours — have intensively investigated the molecular mechanisms through which cancer cells acquire gross chromosomal alterations, and how these abnormalities can be tolerated (which does not occur in normal, non-transformed cells) (Castedo et al.).

One paper published a few years ago in Nature Genetics (Zack et al.) studied somatic copy number alterations in 4,934 cancers from The Cancer Genome Atlas Pan-Cancer data set. This was the first attempt to investigate aneuploidy in a systematic manner across such a large number of clinical samples, and it culminated in the discovery of recurrent patterns of alterations in somatic copy number. Perhaps the most surprising finding of this work, however, was that whole-genome duplication (tetraploidization) was detected in as many as 37% of cancer specimens analysed. Notably, whole-genome duplication correlated with particularly high rates of other somatic copy number alterations, as well as with several unrelated oncogenic events (such as mutations in tumour protein p53 (TP53)) (Zack et al.).

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  1. Lorenzo Galluzzi and Guido Kroemer Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France.,

    Lorenzo Galluzzi & Guido Kroemer

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  1. Lorenzo Galluzzi
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  2. Guido Kroemer
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Correspondence to Lorenzo Galluzzi or Guido Kroemer.

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Galluzzi, L., Kroemer, G. A four-lane highway to cancer. Nat Rev Mol Cell Biol 17, 398 (2016). https://doi.org/10.1038/nrm.2016.73

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