title: The functional cancer map: a systems-level synopsis of genetic deregulation in cancer.
abstract: BACKGROUND
  Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies.
  
  
  METHODS
  Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors.
  
  
  RESULTS
  We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were 'ECM-receptor interaction', 'Complement and Coagulation cascades', and 'PPAR signaling pathway'.
  
  
  CONCLUSIONS
  The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.
authors: Department of Medicine I, Johannes Gutenberg University, Mainz, Germany. kruppm@uni-mainz.de
authors: Markus
authors: M
authors: Krupp
authors: Thorsten
authors: T
authors: Maass
authors: Jens U
authors: JU
authors: Marquardt
authors: Frank
authors: F
authors: Staib
authors: Tobias
authors: T
authors: Bauer
authors: Rainer
authors: R
authors: König
authors: Stefan
authors: S
authors: Biesterfeld
authors: Peter R
authors: PR
authors: Galle
authors: Achim
authors: A
authors: Tresch
authors: Andreas
authors: A
authors: Teufel
mesh_terms: D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D010802:Phylogeny