Global Histone Modifications in Breast Cancer Correlate with Tumor Phenotypes, Prognostic Factors, and Patient Outcome
Published OnlineFirst April 14, 2009; DOI: 10.1158/0008-5472.CAN-08-3907 Research Article Global Histone Modifications in Breast Cancer Correlate with Tumor Phenotypes, Prognostic Factors, and Patient Outcome Somaia E. Elsheikh,1,7 Andrew R. Green,1 Emad A. Rakha,1 Des G. Powe,1 Rabab A. Ahmed,1,8 Hilary M. Collins,2 Daniele Soria,3 Jonathan M. Garibaldi,3 Claire E. Paish,1 Amr A. Ammar,7 Matthew J. Grainge,4 Graham R. Ball,6 Magdy K. Abdelghany,2,9 Luisa Martinez-Pomares,5 David M. Heery,2 and Ian O. Ellis1 1Department of Histopathology, School of Molecular Medical Sciences, University of Nottingham and Nottingham Universities Hospital Trust, Schools of 2Pharmacy and 3Computer Science, 4Division of Epidemiology and Public Health, and 5School of Molecular Medical Sciences, Institute of Infection, Immunity and Inflammation, University of Nottingham; 6Division of Life Sciences, Nottingham Trent University, Nottingham, United Kingdom; 7Department of Pathology, Faculty of Medicine, Menoufyia University, Menoufyia, Egypt; 8Department of Pathology, Faculty of Medicine, Asuit University, Asuit, Egypt; and 9Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt Abstract Introduction Post-translational histone modifications are known to be Breast cancer is a heterogeneous disease ranging from altered in cancer cells, and loss of selected histone acetylation premalignant hyperproliferation to invasive and metastatic carci- and methylation marks has recently been shown to predict nomas (1). Disease progression is poorly understood but is likely patient outcome in human carcinoma. Immunohistochemistry due to the accumulation of genetic mutations leading to was used to detect a series of histone lysine acetylation widespread changes in gene expression and, in particular, affecting (H3K9ac, H3K18ac, H4K12ac, and H4K16ac), lysine methyla- the expression of tumor suppressors and oncogenes (2).
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