Abstract
Abstract Overview: One of the main challenges facing oncology is the identification of highly restricted, cancer-specific biomarkers for use in early diagnostics, prognostics, patient stratification and as potential therapeutic targets, including immunotherapeutic and small drug targets. Germ line genes are normally only expressed in the reproductive organs and meiosis-specific genes are normally only activated within the foetal oocytes and/or the spermatocytes in adult males. Our work has been based on the hypothesis that these germ line genes become activated in cancers, driving the oncogenic process and serving as clinically relevant biomarkers / targets. Our approach and relevance to ovarian cancer: We have taken an in silico approach to identify human meiotic and germ line genes. We have used novel computational tools to determine whether these genes are restricted to immunologically privileged / germ line tissues in healthy adults and whether they are activated in human tumours. We have also experimentally validated these expression profiles. Our meta-analysis of human cancer gene expression microarray data reveals high incidences of germ line gene activation in human ovarian cancers1,2, suggesting that these cancers more readily take on a germ line state than other human tumour types. Subsequent laboratory-based work indicates that some of these genes are required for ovarian cancer cell proliferation. Conclusions / perspectives: Evidence is starting to emerge that human cancers adopt a more germ line state as part of the oncogenic process. In a Drosophila melanogaster brain tumour model it has been demonstrated that these germ line genes are required for oncogenesis; moreover, aberrantly expressed human germ line genes are required for the proliferation of human cancer cells in vitro. Indeed, it has been postulated that cancer cells become ‘addicted’ to these germ line factors, making them a very poorly explored pool of potential drug targets. Additionally, recent work has demonstrated that a sub-group of germ line genes can be used as powerful markers for the stratification of lung cancer patients. Our finding that ovarian cancers take on a highly active germ line transcriptional profile suggests that this might provide an important source of biomarkers and therapeutic targets for ovarian cancers. 1 Feichtinger et al. (2012) Meta-analysis of clinical data using human meiotic genes identifies a novel cohort of highly restricted cancer-specific marker genes. Oncotarget 3: 843-853. 2 Feichtionger et al. (2014) Meta-analysis of expression of l(3)mbt tumour-associated germline genes supports the model that a soma-to-germline transition is a hallmark of human cancers. Int. J. Cancer 134: 2359-2365. Citation Format: Ramsay McFarlane. Meta-analysis of cancer microarray data sets reveals a germ line expression profile in ovarian cancers: new biomarkers and potential drug targets [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-TECH-1118.
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