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Profiling of Epigenetic Features in Clinical Samples Reveals Novel Widespread Changes in Cancer

1
Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy
2
Novel Diagnostics Program, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
3
Biobank for Translational Medicine Unit (B4MED), Department of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
4
Division of Pathology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
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Division of Otolaryngology Head & Neck Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
6
Unit of Gynecological Oncology Research, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(5), 723; https://doi.org/10.3390/cancers11050723
Received: 29 March 2019 / Revised: 9 May 2019 / Accepted: 20 May 2019 / Published: 24 May 2019
(This article belongs to the Collection Histone Modification in Cancer)
Aberrations in histone post-translational modifications (PTMs), as well as in the histone modifying enzymes (HMEs) that catalyze their deposition and removal, have been reported in many tumors and many epigenetic inhibitors are currently under investigation for cancer treatment. Therefore, profiling epigenetic features in cancer could have important implications for the discovery of both biomarkers for patient stratification and novel epigenetic targets. In this study, we employed mass spectrometry-based approaches to comprehensively profile histone H3 PTMs in a panel of normal and tumoral tissues for different cancer types, identifying various changes, some of which appear to be a consequence of the increased proliferation rate of tumors, while others are cell-cycle independent. Histone PTM changes found in tumors partially correlate with alterations of the gene expression profiles of HMEs obtained from publicly available data and are generally lost in culture conditions. Through this analysis, we identified tumor- and subtype-specific histone PTM changes, but also widespread changes in the levels of histone H3 K9me3 and K14ac marks. In particular, H3K14ac showed a cell-cycle independent decrease in all the seven tumor/tumor subtype models tested and could represent a novel epigenetic hallmark of cancer. View Full-Text
Keywords: epigenetics; histone post-translational modifications; mass spectrometry; proteomics; cancer; cell cycle; cell culture epigenetics; histone post-translational modifications; mass spectrometry; proteomics; cancer; cell cycle; cell culture
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Noberini, R.; Restellini, C.; Savoia, E.O.; Raimondi, F.; Ghiani, L.; Jodice, M.G.; Bertalot, G.; Bonizzi, G.; Capra, M.; Maffini, F.A.; Tagliabue, M.; Ansarin, M.; Lupia, M.; Giordano, M.; Osti, D.; Pelicci, G.; Chiocca, S.; Bonaldi, T. Profiling of Epigenetic Features in Clinical Samples Reveals Novel Widespread Changes in Cancer. Cancers 2019, 11, 723.

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