PO-113 Investigation of the role of IRF4 in melanoma cells

• Published in: ESMO open Vol. 3; no. Suppl 2; pp. A64 - A65
• Main Authors: Emre, T, Sobhiafshar, U, Yildiz, N, Tufan, B, Yilmaz, E, Ayhan, M, Erkan, E, Yerinde, C
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-07-2018
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1136/esmoopen-2018-EACR25.154

IntroductionWhile much progress has been made in melanoma treatment in the recent years, melanoma still remains a generally lethal disease at the metastatic stage. Therefore, discovery of additional critical target genes and pathways, and the development of novel therapeutic approaches remain a priority. Like most cancers, abnormal gene regulatory and epigenetic mechanisms are also linked to melanomas.The transcription factor interferon regulatory factor 4 (IRF4) was discovered as a factor implicated in immunoglobulin expression in B-cells, and was later shown to perform central roles in immune cell development and function. We have previously demonstrated the critical role of IRF4 in a variety of B-cell cancer cells, and identified its mechanisms of action. These and related work suggested IRF4 pathways as therapy targets in cancer. Several studies implicate IRF4 expression and function also in non-immune cells, such as melanocytes. For instance, a number of genome-wide genetic studies associated variation at the IRF4 gene with pigmentation phenotypes and skin cancers. However, despite the observed genetic links and generally high expression, the role of IRF4 in melanoma remains under-studied and poorly understood.Material and methodsWe set out to identify the functions of IRF4 in melanoma cells using genome-wide and cell and molecular biological approaches. We have taken a candidate approach to discover the upstream modulators of IRF4 expression in melanoma cells. In parallel, we have performed localization (ChIP-seq) and transcriptomic (RNA-seq) assays in order to identify the genome-wide targets of IRF4 in melanoma cell lines.Results and discussionsAs upstream regulators of IRF4 expression, we identified a known melanoma master transcription factor and a major signalling pathway with therapeutic targeting options. For downstream targets of IRF4, together with The Cancer Genome Atlas (TCGA) data analyses, our data point to a role of IRF4 in epigenetic regulation of melanoma cells, among other cancer- and development-related pathways. In addition, our preliminary studies implicate IRF4 as a critical factor in melanoma cell proliferation and survival.ConclusionOverall these studies on IRF4 in melanoma cells are complementing mechanistically the available genetic findings in melanoma patient samples, and describing a novel pathway in melanoma cells, with the potential to point to new therapy approaches for melanoma.