DNA Damage Repair and Telomere Length in Normal Breast, Preneoplastic Lesions, and Invasive Cancer
Autor: | Christophe M. Raynaud, Frédéric Commo, Paolo Nuciforo, Juana Hernandez, M. C. Mathieu, Frédérique P. Llorca, Suzette Delaloge, Jean-Charles Soria, Fabrice Andre, Laure Sabatier |
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Rok vydání: | 2010 |
Předmět: |
Adult
Cancer Research Pathology medicine.medical_specialty DNA Repair DNA damage DNA repair Breast Neoplasms In situ hybridization medicine.disease_cause Histones Breast cancer Humans Medicine Neoplasm Invasiveness Breast Aged business.industry Cancer Middle Aged Telomere medicine.disease Oncology Immunohistochemistry Female business Carcinogenesis Precancerous Conditions DNA Damage |
Zdroj: | American Journal of Clinical Oncology. 33:341-345 |
ISSN: | 0277-3732 |
Popis: | 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 gamma-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. |
Databáze: | OpenAIRE |
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