TY - JOUR A1 - Catchpole, Gareth A1 - Platzer, Alexander A1 - Weikert, Cornelia A1 - Kempkensteffen, Carsten A1 - Johannsen, Manfred A1 - Krause, Hans A1 - Jung, Klaus A1 - Miller, Kurt A1 - Willmitzer, Lothar A1 - Selbig, Joachim A1 - Weikert, Steffen T1 - Metabolic profiling reveals key metabolic features of renal cell carcinoma JF - Journal of cellular and molecular medicine : a journal of translational medicine N2 - Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. alpha-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC. KW - kidney cancer KW - metabolism KW - metabolomics KW - metastasis Y1 - 2011 U6 - https://doi.org/10.1111/j.1582-4934.2009.00939.x SN - 1582-1838 VL - 15 IS - 1 SP - 109 EP - 118 PB - Wiley-Blackwell CY - Malden ER - TY - JOUR A1 - Roessner, Ute A1 - Luedemann, A. A1 - Brust, D. A1 - Fiehn, Oliver A1 - Linke, Thomas A1 - Willmitzer, Lothar A1 - Fernie, Alisdair R. T1 - Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems Y1 - 2001 SN - 1040-4651 ER - TY - JOUR A1 - Lisec, Jan A1 - Steinfath, Matthias A1 - Meyer, Rhonda C. A1 - Selbig, Joachim A1 - Melchinger, Albrecht E. A1 - Willmitzer, Lothar A1 - Altmann, Thomas T1 - Identification of heterotic metabolite QTL in Arabidopsis thaliana RIL and IL populations N2 - Two mapping populations of a cross between the Arabidopsis thaliana accessions Col-0 and C24 were cultivated and analyzed with respect to the levels of 181 metabolites to elucidate the biological phenomenon of heterosis at the metabolic level. The relative mid-parent heterosis in the F-1 hybrids was <20% for most metabolic traits. The first mapping population consisting of 369 recombinant inbred lines (RILs) and their test cross progeny with both parents allowed us to determine the position and effect of 147 quantitative trait loci (QTL) for metabolite absolute mid-parent heterosis (aMPH). Furthermore, we identified 153 and 83 QTL for augmented additive (Z(1)) and dominance effects (Z(2)), respectively. We identified putative candidate genes for these QTL using the ARACYC database (http://www.arabidopsis.org/ biocyc), and calculated the average degree of dominance, which was within the dominance and over-dominance range for most metabolites. Analyzing a second population of 41 introgression lines (ILs) and their test crosses with the recurrent parent, we identified 634 significant differences in metabolite levels. Nine per cent of these effects were classified as over-dominant, according to the mode of inheritance. A comparison of both approaches suggested epistasis as a major contributor to metabolite heterosis in Arabidopsis. A linear combination of metabolite levels was shown to significantly correlate with biomass heterosis (r = 0.62). Y1 - 2009 UR - http://www3.interscience.wiley.com/cgi-bin/issn?DESCRIPTOR=PRINTISSN&VALUE=0960-7412 U6 - https://doi.org/10.1111/j.1365-313X.2009.03910.x SN - 0960-7412 ER -