Abstract 5268: The expression of lemur tyrosine kinase-3 in high grade pediatric tumors

High grade gliomas are the most common primary brain tumors in adults, but also occur in childhood, with a poor prognosis in all age groups . Lemur tyrosine kinase 3 (LMTK3) is a transmembrane tyrosine kinase that seems to play a pivotal role in oncogenesis in breast cancer. It regulates the estrogen receptor alpha and is evolutionarily selected for in humans compared to non-human primates. LMTK3 expression levels were strongly associated with survival and therapy response.This study assesses the role of LMTK3 in pediatric high grade brain tumors at both the protein and mRNA levels. We initially assessed by immunohistochemistry (IHC) the expression levels of LMTK3 in well described cohorts of patient specimens with brain cancer. First, we performed an IHC analysis using a brain tumor tissue microarray (TMA) purchased from US Biomax (#T175), in order to examine the LMTK3 levels in a variety of brain tumors. Preliminary analysis revealed variable LMTK3 expression levels in brain tissue, scored as negative, low, moderate and high. We demonstrate that LMTK3 appears to be expressed at low levels at normal brain tissue samples and epithelial meningioma tissues (benign tumors). On the contrary, LMTK3 was expressed at different levels in cases with grade 2 or grade 4 gliomas. Further immunohistochemical analysis was therefore undertaken on a selection of TMAs containing pediatric high grade gliomas. Genome wide gene expression analysis (using the Affymetrix U133plus2 chip) previously undertaken on a cohort of pediatric high grade gliomas demonstrated measurable LMTK3 mRNA expression in many samples. Our preliminary analysis was correlated with various tumor characteristics that are available in Nottingham datasets (including demographic and overall survival data). In conclusion, LMTK3 is expressed in pediatric high grade gliomas and may have differential expression depending on the histological grade of the tumor. This work will lead to larger scale studies to elucidate the exact role of LMTK3 in high grade brain neoplasms. Citation Format: Nektarios K. Mazarakis, Stuart Smith, Aikaterini Vraka, Donald Macarthur, Richard Grundy, Justin Stebbing, George Giamas. The expression of lemur tyrosine kinase-3 in high grade pediatric tumors. [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 5268. doi:10.1158/1538-7445.AM2014-