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A ‘DNA replication’ signature of progression and negative outcome in colorectal cancer

Oncogene volume 29, pages 876–887 (2010)Cite this article

A Corrigendum to this article was published on 08 April 2010

Abstract

Colorectal cancer is one of the most frequent cancers worldwide. As the tumor-node-metastasis (TNM) staging classification does not allow to predict the survival of patients in many cases, additional prognostic factors are needed to better forecast their outcome. Genes involved in DNA replication may represent an underexplored source of such prognostic markers. Indeed, accidents during DNA replication can trigger ‘replicative stress’, one of the main features of cancer from earlier stages onward. In this study, we assessed the expression of 47 ‘DNA replication’ genes in primary tumors and adjacent normal tissues from a homogeneous series of 74 patients. We found that genes coding for translesional (TLS) DNA polymerases, initiation of DNA replication, S-phase signaling and protection of replication forks were significantly deregulated in tumors. We also observed that the overexpression of either the MCM7 helicase or the TLS DNA polymerase POLQ (if also associated with a concomitant overexpression of firing genes) was significantly related to poor patient survival. Our data suggest the existence of a ‘DNA replication signature’ that might represent a source of new prognostic markers. Such a signature could help in understanding the molecular mechanisms underlying tumor progression in colorectal cancer patients.

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Acknowledgements

We thank the ‘GSO/3R’ Consortium for helpful discussions. We thank B Orsetti for CGH experiments (GSO aCGH platform, CRLCC Montpellier). We also acknowledge JJ Maoret (Q-PCR platform, IFR31, Toulouse), as well as F Viala and S Mazeres (IPBS, Toulouse) for iconography and technical assistance, respectively. This study was supported by INCa (Canceropole GSO, grant ACI ‘Genetic instability as a negative outcome’ 2004/07 and 2008/09 to CC; grants to JS, DT and PP).

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  1. M-J Pillaire and J Selves: These authors have equally contributed.

Authors and Affiliations

  1. Department Biology of Cancer, Genetic Instability and Cancer Group, Institute of Pharmacology and Structural Biology, UMR5089 CNRS, University of Toulouse, University Paul Sabatier, Toulouse, France

    M-J Pillaire, A Bieth, J-S Hoffmann & C Cazaux

  2. Federation of Digestive Cancerology and Department of Anatomo-pathology, INSERM U563, University of Toulouse, University Paul Sabatier, Toulouse, France

    J Selves, K Gordien, M Danjoux & R Guimbaud

  3. Service of Epidemiology, INSERM U558, Faculty of Medicine, University of Toulouse, University Paul Sabatier, Allées Jules Guesde, Toulouse, France

    P-A Gouraud, C Gentil & C Do

  4. aCGH GSO Canceropole Platform, INSERM U868, Val d’Aurelle, Montpellier, France

    V Negre

  5. Laboratory of Cellular and Molecular Biology of Cell Proliferation Control, UMR 5099 CNRS, University of Toulouse, University Paul Sabatier, Toulouse, France

    D Trouche

  6. Institute of Human Genetics UPR1142 CNRS, Montpellier, France

    P Pasero & M Méchali

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  1. M-J Pillaire
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Correspondence to C Cazaux.

Additional information

C Cazaux and JS Hoffmann share the leadership of the Genetic Instability and Cancer Group.

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Pillaire, MJ., Selves, J., Gordien, K. et al. A ‘DNA replication’ signature of progression and negative outcome in colorectal cancer. Oncogene 29, 876–887 (2010). https://doi.org/10.1038/onc.2009.378

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