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Frequent intragenic rearrangements of DPYD in colorectal tumours

The Pharmacogenomics Journal volume 15, pages 211–218 (2015)Cite this article

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Abstract

Dihydropyrimidine dehydrogenase is a crucial enzyme for the degradation of 5-fluorouracil (5FU). DPYD, which encodes dihydropyrimidine dehydrogenase, is prone to acquire genomic rearrangements because of the presence of an intragenic fragile site FRA1E. We evaluated DPYD copy number variations (CNVs) in a prospective series of 242 stage I–III colorectal tumours (including 87 patients receiving 5FU-based treatment). CNVs in one or more exons of DPYD were detected in 27% of tumours (deletions or amplifications of one or more DPYD exons observed in 17% and 10% of cases, respectively). A significant relationship was observed between the DPYD intragenic rearrangement status and dihydropyrimidine dehydrogenase (DPD) mRNA levels (both at the tumour level). The presence of somatic DPYD aberrations was not associated with known prognostic or predictive biomarkers, except for LOH of chromosome 8p. No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer.

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Acknowledgements

We thank the French Research Ministry (Programme Hospitalier de Recherche Clinique) for financial support and the Ligue Nationale Contre le Cancer (CIT programme) for PIK3CA, APC and CIMP analyses.

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Authors and Affiliations

  1. Department of Clinical Chemistry and Pediatrics, Academic Medical Center, University of Amsterdam, Emma Children’s Hospital, Amsterdam, The Netherlands

    A B P van Kuilenburg, J Meijer & R C M Hennekam

  2. Centre Antoine Lacassagne, Laboratoire d'Oncopharmacologie, Nice cedex 2, France

    M-C Etienne-Grimaldi & G Milano

  3. Unité de cancérologie digestive Hôpital Archet II, Nice cedex, France

    A Mahamat

  4. Hôpital Georges Pompidou, Paris, France

    P Laurent-Puig

  5. INSERM UMR_S910, Marseille, France

    S Olschwang

  6. Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    M-P Gaub

  7. Hôpital de L’Archet-CHU de Nice, Nice, France

    D Benchimol

  8. Hôpital Tenon, Université Pierre et Marie Curie, Paris, France

    S Houry

  9. Department of Surgery, University Hospital and Joseph Fourier University, Grenoble, France

    C Letoublon & J-L Faucheron

  10. Université Claude Bernard Lyon 1, Pierre bénite cedex, France

    F-N Gilly

  11. CHU Clermont Ferrand, Clermont Ferrand Cedex 1, France

    D Pezet

  12. Department of medical Oncology, Saint Antoine Hospital, Paris, France

    T Andre

  13. Department of Surgery, CHU de Nice, Nice, France

    A Abderrahim-Ferkoune

  14. MRC-Holland, Amsterdam, The Netherlands

    R Vijzelaar

  15. Centre Hospitalier Universitaire de Toulouse, Université Toulouse III Paul Sabatier, Toulouse, France

    B Pradere

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  1. A B P van Kuilenburg
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Correspondence to A B P van Kuilenburg.

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Raymon Vijzelaar is employed by MRC-Holland that manufactures MLPA probemixes. The remaining authors declare no conflict of interest.

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van Kuilenburg, A., Etienne-Grimaldi, MC., Mahamat, A. et al. Frequent intragenic rearrangements of DPYD in colorectal tumours. Pharmacogenomics J 15, 211–218 (2015). https://doi.org/10.1038/tpj.2014.68

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