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 language | English |
|---|---|
| Pages (from-to) | 341-345 |
| Number of pages | 5 |
| Journal | American Journal of Clinical Oncology: Cancer Clinical Trials |
| Volume | 33 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Aug 2010 |
| Externally published | Yes |
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Keywords
- Carcinogenesis
- DNA damage repair
- Telomeres
ASJC Scopus subject areas
- Oncology
- Cancer Research
- Medicine(all)
Cite this
DNA damage repair and telomere length in normal breast, preneoplastic lesions, and invasive cancer. / Raynaud, Christophe M.; Hernandez, Juana; Llorca, Frédérique P.; Nuciforo, Paolo; Mathieu, Marie Christine; Commo, Frederic; Delaloge, Suzette; Sabatier, Laure; André, Fabrice; Soria, Jean Charles.
In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 33, No. 4, 01.08.2010, p. 341-345.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - DNA damage repair and telomere length in normal breast, preneoplastic lesions, and invasive cancer
AU - Raynaud, Christophe M.
AU - Hernandez, Juana
AU - Llorca, Frédérique P.
AU - Nuciforo, Paolo
AU - Mathieu, Marie Christine
AU - Commo, Frederic
AU - Delaloge, Suzette
AU - Sabatier, Laure
AU - André, Fabrice
AU - Soria, Jean Charles
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
KW - Carcinogenesis
KW - DNA damage repair
KW - Telomeres
UR - http://www.scopus.com/inward/record.url?scp=77956635152&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956635152&partnerID=8YFLogxK
U2 - 10.1097/COC.0b013e3181b0c4c2
DO - 10.1097/COC.0b013e3181b0c4c2
M3 - Article
C2 - 19884805
AN - SCOPUS:77956635152
VL - 33
SP - 341
EP - 345
JO - American Journal of Clinical Oncology
JF - American Journal of Clinical Oncology
SN - 0277-3732
IS - 4
ER -