Aim: Here, we set out to establish whether endogenous γ-H2AX is a biomarker in triple-negative breast cancer. Methods: We explored the association of γ-H2AX with mutation status and sensitivity to 139 different anticancer drugs in up to 41 breast cancer cell lines. Further, we correlated γ-H2AX expression in breast cancer tumor tissues with telomere length. Results: γ-H2AX positive breast cancer cells exhibit more mutations, and - when p53 mutated - have shorter telomeres. In breast cancer patients γ-H2AX is also related to shorter telomeres, which was in turn associated with poorer prognosis of triple-negative breast cancer patients. Conclusion: Thus, endogenous γ-H2AX is associated with short telomeres, which might offer a specific target for therapy for triple-negative breast cancer patients.

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Keywords breast neoplasm, phosphorylated histone 2AX, telomere dysfunction, triple negative
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Journal Biomarkers in Medicine
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Nagelkerke, A, van Kuijk, S.J.A, Martens, J.W.M, Sweep, F.C, Hoogerbrugqe, N, Bussink, J, & Span, P.N. (2015). Poor prognosis of constitutive γ-H2AX expressing triple-negative breast cancers is associated with telomere length. Biomarkers in Medicine, 9(4), 383–390. doi:10.2217/bmm.15.2