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

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34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)341-345
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume33
Issue number4
DOIs
Publication statusPublished - 1 Aug 2010
Externally publishedYes

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Keywords

  • Carcinogenesis
  • DNA damage repair
  • Telomeres

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

Raynaud, C. M., Hernandez, J., Llorca, F. P., Nuciforo, P., Mathieu, M. C., Commo, F., Delaloge, S., Sabatier, L., André, F., & Soria, J. C. (2010). DNA damage repair and telomere length in normal breast, preneoplastic lesions, and invasive cancer. American Journal of Clinical Oncology: Cancer Clinical Trials, 33(4), 341-345. https://doi.org/10.1097/COC.0b013e3181b0c4c2