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Why is p53-inducible gene 3 rarely affected in cancer?

Oncogene volume 29, page 5220 (2010)Cite this article

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Dear Sir,

We read with great interest the work on the contribution of the p53-inducible gene 3 (PIG3) to the early cellular response to DNA damage (Lee et al., 2010). PIG3 was considered until now as a p53-dependent proapoptotic gene mediating reactive oxygen species (ROS) production. p53 regulates PIG3 through a polymorphic pentanucleotide sequence. An individual's constitution or deregulation of this repetitive sequence, by microsatellite instability (MSI), was postulated as potential mechanisms for cancer susceptibility (Contente et al., 2002). Collectively, we and others (Gorgoulis et al., 2004 and references therein), along with our additional unpublished data from 114 lung tumors (7% loss of heterozygosity (LOH) and 0.9% MSI), have shown that MSI and LOH rarely affect this locus in various common tumors, whereas rare pentanucleotide alleles are not associated with cancer risk. An alternative splicing of PIG3 mRNA resulting in an unstable truncated variant (Nicholls et al., 2004) could represent another PIG3 inactivation mechanism. Nevertheless, our unpublished work in a subset of the previously mentioned lung tumors for potential PIG3 alternative splicing deregulation favoring the truncated form was not found. On contrary, the full-length transcript was predominantly found to be increased in tumor counterparts (96.7%). Collectively, these results raise the question: why is PIG3 rarely affected in cancer?

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Acknowledgements

We acknowledge the financial support from the European Commission (FP7 projects GENICA and INFLA-CARE) and the SARG-NKUA (Grant numbers 70/3/1703, 70/4/9913, 70/4/4281).

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Authors and Affiliations

  1. Department of Histology and Embryology, Molecular Carcinogenesis Group, School of Medicine, University of Athens, Athens, Greece

    A Kotsinas, I S Pateras, P S Galanos & V G Gorgoulis

  2. Department of Biological Chemistry, School of Medicine, University of Athens, Athens, Greece

    M V Karamouzis

  3. First Department of Propedeutic and Internal Medicine, School of Medicine, University of Athens, Athens, Greece

    P P Sfikakis

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  1. A Kotsinas
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  2. I S Pateras
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  4. M V Karamouzis
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  5. P P Sfikakis
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  6. V G Gorgoulis
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Correspondence to V G Gorgoulis.

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Kotsinas, A., Pateras, I., Galanos, P. et al. Why is p53-inducible gene 3 rarely affected in cancer?. Oncogene 29, 5220 (2010). https://doi.org/10.1038/onc.2010.263

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