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Repair of double strand DNA breaks (DSBs) is pivotal in maintaining normal cell division and disruption of this system has been shown to be a key factor in carcinogenesis. Loss of expression of the DSB repair proteins have previously been shown to be associated with poorer survival in colorectal cancer. We wished to ascertain the relationship of altered expression of the DSB repair proteins γ-H2AX (gamma-H2AX), ATM and Ku70 with biological and clinico-pathological features of colorectal cancer. 908 tumours from the VICTOR clinical trial of stage II/III colorectal cancer were analysed for expression of γ-H2AX, ATM and Ku70 using immunohistochemistry. Expression levels were correlated with CIN and with disease-free survival, correcting for microsatellite instability, BRAF/KRAS mutation status, Dukes stage, chemo/radiotherapy, age, gender and tumour location. Down-regulated Ku70 expression was associated with chromosomal instability (p=0.029) in colorectal cancer. Reduced ATM expression was an independent marker of poor disease-free survival (HR=1.67, 95% CI 1.11-2.50, p=0.015). For Ku70, further studies are required to investigate the potential relationship of non-homologous end joining with chromosomal instability. Loss of ATM expression might serve as a biomarker of poor prognosis in colorectal cancer.

Original publication

DOI

10.18632/oncotarget.694

Type

Journal article

Journal

Oncotarget

Publication Date

11/2012

Volume

3

Pages

1348 - 1355

Keywords

Antigens, Nuclear, Ataxia Telangiectasia Mutated Proteins, Biomarkers, Tumor, Cell Cycle Proteins, Chromosomal Instability, Colorectal Neoplasms, DNA Breaks, Double-Stranded, DNA Repair, DNA-Binding Proteins, Disease-Free Survival, Down-Regulation, Genotype, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Ku Autoantigen, Polymorphism, Genetic, Prognosis, Protein-Serine-Threonine Kinases, Randomized Controlled Trials as Topic, Tumor Suppressor Proteins