Abstract 1371: Histone lysine trimethylation or acetylation in sporadic breast tumor and matched normal tissue

Breast cancer is responsible of cancer mortality in women worldwide. The challenge in carcinogenesis is to predict tumor progression. Epigenetics open new perspectives in this field. It was demonstrated that epigenetic alterations are involved in cancer. DNA methylation or histone modifications can regulate gene transcription. Our goal was to determine the role of different histone marks, such as H3K27me3, H3K4ac and H3K9ac on the expression of a panel of genes involved in breast cancer: BRCA1, ERβ, EZH2, P300, SRC3, ERα and PGR. For this study, we used less than one hundred sporadic breast tumors and matched normal tissues. We performed chromatin immunoprecipitation and Q-PCR. After that, we checked the gene expression assaying RNA with RT-QPCR and proteins with Western blotting. Finally, we demonstrated that H3K4ac marks behaved like H3K27me3 repressive marks. The increase of H3K9ac marks resulted in the overexpression of ERα and P300 genes in the tumors. For the underexpressed genes BRCA1 and ERβ, we found that their repression did not pass through the repressive marks H3K27me3 nor H3K4ac but by other mechanisms perhaps DNA methylation. Then, we used variance analysis and studied interactions between the studied different marks and intrinsic subtypes of breast cancer according to St Gallen International Expert Consensus. Finally, we defined gene-mark couples in each subtypes. At the end, a decision tree was drawn and determined 4 genes (BRCA1, ERα, ERβ, and PGR) and 2 marks (H3K27me3 and H3K4ac) that separated subtypes in the present study. Citation Format: Dominique J. Gallon-Bernard, Gaëlle Judes, Aslihan Dagdemir, Maureen Echegut, Seher Karsli-Ceppioglu, Marjolaine Ngollo, Andre Lebert, Frederique Penault-Llorca, Yves-Jean Bignon. Histone lysine trimethylation or acetylation in sporadic breast tumor and matched normal tissue. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1371. doi:10.1158/1538-7445.AM2014-1371