Abstract 2398: Molecular analysis of histone methyltransferases SUV420H1 and SUV420H2 and their potential as prognostic markers in head and neck cancer
Authors: Ramos Doralina do Amaral Rabello , Ribeiro Beatriz Itai Haupt , Castro Tércia Maria Mendes Lousa de , Ferreira Vívian D'Afonseca da Silva , Takano Gustavo Henrique Soares , Duarte Eliza Carla Barroso , Carneiro Fabiana Pirani , Silva Fábio Pittella 
Published: July 2017

Abstract
The incidence of head and neck cancer as well as its mortality rates continues to increase, evidencing the need for diagnostic and prognostic markers that can improve clinical management of these patients. Histone Methyltransferases (HMT) are responsible for the methylation of histone tails, a mechanism important for the regulation of gene transcription, cell differentiation and proliferation. Although alterations on these enzymes have been associated with many types of cancer, their relationship with head and neck carcinogenesis is not yet understood. SUV420H1 and SUV420H2 are members of the SUV family of HMTs that contain the conserved SET domain, which catalyzes the addition of methyl groups to specific lysine residues, leading to chromatin compaction and gene repression. In the present study, we investigated the tissue expression profile of SUV420H1 and SUV420H2 using immunohistochemistry in 10 formalin-fixed paraffin-embedded human oral cancer samples and adjacent non-tumor tissues. We also investigated the alterations of SUV420H1 and SUV420H2 genes in head and neck cancer with in silico analyses from public databases. Immunohistochemistry revealed moderate to strong SUV420H1 and SUV420H2 expression in the majority of oral cancer cells, mainly with cytoplasmic staining in the invading tumor cells. In silico analyses using data from 530 head and neck squamous cell carcinoma samples (The Cancer Genome Atlas - TCGA, via cBioPortal) revealed that amplification is the most frequent genetic alteration in SUV420H1. Considering all known lysine methyltransferases, SUV420H1 was among the top three with the highest frequency of amplification. For SUV420H2, the frequency for amplification and deletion alterations was similar. The gene expression level of these methyltransferases was also analyzed. SUV420H1 showed a high expression of mRNA in head and neck cancer samples, with a moderate correlation (R: 0.588) between genetic copy number alteration and mRNA level. SUV420H2 did not show significant altered expression. In addition, SUV420H1 mRNA overexpression was associated with decreased overall survival in head and neck cancer patients (p: 0.0233). Since these enzymes are important in chromatin compaction and gene transcription repression, an increase in their expression level, as detected in this study, could lead to changes in histone methylation pattern, resulting in aberrant silencing of genes essential to maintain normal cellular function, such as tumor suppressor genes. Taken together, our data indicates a possible role of SUV420H1 in head and neck carcinogenesis, with the potential to be used as a prognostic marker for the disease.
Citation Format: Doralina do Amaral Rabello Ramos, Beatriz Itai Haupt Ribeiro, Tércia Maria Mendes Lousa de Castro, Vívian D'Afonseca da Silva Ferreira, Gustavo Henrique Soares Takano, Eliza Carla Barroso Duarte, Fabiana Pirani Carneiro, Fábio Pittella Silva. Molecular analysis of histone methyltransferases SUV420H1 and SUV420H2 and their potential as prognostic markers in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2398. doi:10.1158/1538-7445.AM2017-2398