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Functional tumour genomics using metabolomic profiling

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Using metabolites for cancer profiling

Cancer detection and treatment presents a challenge to the scientific community, driving research into the development and evaluation of novel methods. Alongside that notion, a European initiative used cancer cell metabolism as a means of characterising and visualising tumours.

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Metabolomics – the unique chemical fingerprinting of cells – is emerging as a new powerful method of determining cellular physiology. It is advantageous compared to mRNA or proteomic profiling in that it can discriminate single gene alterations and identify metabolite biomarkers which can function as surrogates for the genetic event. Research in the field has generated metabolome profiles from gene deletion mutants and used them as a functional genomics tool. This has provided scientists with the ability to use metabolomic data in order to understand the structure of metabolic networks and link the metabolome to the genome. To this end, the key goal of the EU-funded ‘Functional tumour genomics using metabolomic profiling’ (Futugemet) project was to define the metabolic profiles associated with the expression of specific genes in tumour cells. To achieve that, project scientists knocked down various genes in cell lines and using NMR spectroscopy and mass spectrometry they analysed the metabolic profile of the cells. Results demonstrated a clear correlation between tumour cell metabolism and gene expression changes, emphasising the value of metabolic profiling for cancer detection. Application of this method to patient samples has the potential to identify abnormalities in metabolic pathways and provide insight into the role of certain metabolites in tumour cell physiology. Furthermore, scientists evaluated metabolic-based methods for detecting cancer such as the in vivo PET imaging tracing the fate of 11C-acetate during fatty acid biosynthesis. They discovered that the increased lipid synthesis observed in cancer cells was due to alterations in the metabolic pathway of fatty acids. In vivo experiments also revealed that acetate was initially taken up by all the tissues, but one hour after injection it was only retained in tissues where conversion into lipids had occurred such as in tumours. Futugemet developed a metabolome-based approach for defining the metabolic network structure in tumour cells and how it is related to expression of different oncogenes and tumour suppressor genes. The identification of metabolites that are correlated with common genetic changes in cancer cells will facilitate the design of new molecular imaging methods for detecting tumours and hopefully the development of new drugs.

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