DNA damage repair and telomere length in normal breast, preneoplastic lesions, and invasive cancer

Christophe M. Raynaud, Juana Hernandez, Frédérique P. Llorca, Paolo Nuciforo, Marie Christine Mathieu, Frederic Commo, Suzette Delaloge, Laure Sabatier, Fabrice André, Jean Charles Soria

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    39 Citations (Scopus)

    Résumé

    Objectives: Carcinogenesis is a multistep process involving the accumulation of genetic and molecular abnormalities. It has been suggested that there is a relationship between telomere attrition in the early stages of carcinogenesis and activation of the DNA damage response machinery. We explored telomere length modification and damage response pathway activation at 3 steps of breast carcinogenesis. Methods: We carried out a retrospective immunohistochemical analysis of pathway ataxia telangiectasia mutated (p-ATM) (series 1981) and +-H2AX (series 139) levels in normal breast, preneoplastic lesions, and invasive carcinoma. Fluorescent in situ hybridization was used to analyze telomere length at each stage. Results: ATM was activated in 45% of normal tissue samples, 70% of preneoplastic lesions, and 14% of breast carcinomas. The increase in ATM activation, between normal tissues and preneoplasia, was not significant (P =0.095), whereas, ATM repression between preneoplasia and cancer was significant (P = 0.0023). Telomeres in preneoplastic lesions were more frequently shorter than those in normal tissues (P = 0.0116). Finally, telomere lengths were long in 38.9% and very short in 38.9% of breast carcinomas (P = 0.0087 for comparisons with preneoplastic lesions). Conclusions: This study suggests that a major defect in DNA repair occurs between preneoplasia and breast cancer. This defect is associated with changes in telomere length between the preneoplastic and the cancer stage.

    langue originaleAnglais
    Pages (de - à)341-345
    Nombre de pages5
    journalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
    Volume33
    Numéro de publication4
    Les DOIs
    étatPublié - 1 août 2010

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