Participate in the network transformations associated with tumorigenesis. A high level view of network rearrangements can be seen by comparing modules in AN and TU. Many significant overlaps were seen indicating that the two tissues were far from randomly organized with respect to each other. Closer examination revealed support for the disruption and creation of co-expression networks found with gene-gene differential correlation data. For example, the genes in the largest module in AN significantly overlapped the genes in eight different TU modules as well as genes that could not be placed in the TU network, consistent with disruption of the AN-turquoise module. Similarly, genes in the largest module in TU, overlapped genes in 10 AN modules as well as genes in AN-grey, consistent with 
the creation of TU-turquoise as part of HCC tumorigenesis. Consistent with the above interpretation of the AN and TU module overlaps was the finding that the differentially correlated genes were enriched in many of the modules. For example, 22 of the 25 AN modules and 13 of the 20 TU modules were enriched for genes containing differentially correlated genes, indicating that a majority of the subnetworks in the AN tissue representing many different biological functions were disrupted as a result of the formation and progression of the tumor, resulting in a higher level re-organization. To assess possible biological functions represented by the networks, each module was tested for over-representation of genes from individual gene ontology categories. Given the large scale reorganizations between AN and TU, GO terms that were most significantly enriched for each module compared to all other modules were defined. The purpose of this was to begin to define biological pathways that were uniquely disrupted in AN tissue and uniquely Orbifloxacin created in TU tissue. Examples of this are the findings that components of the ribosome were uniquely enriched in the TU-grey60 module, and aspects of macrophage function were uniquely enriched in the AN-coral module. In both cases these terms were not enriched in any other module of either tissue. Many unique or relative enrichments of GO terms were found for 14 of the 25 AN modules and 12 of the 21 TU modules representing a broad array of biological functions coherently represented in the networks and altered between tissues in HCC tumorigenesis. Ribosome components have been clearly implicated in tumor initiation and progression in numerous cancer types. In particular it has been argued that altered translation Cinoxacin facilitates expression of many proliferation associated genes and may also regulate the endothelial to mesenchymal transition which is thought to be important in invasion and metastasis. The enrichment of TU-survival genes in TU-grey60 and TU-lightyellow suggests that translation and ribosome biogenesis were selected for alteration during tumorigenesis, but remained rate limiting factors in progression. Copy number aberrations are widely observed in solid tumors and are likely the result of altered fidelity of DNA replication, repair, checkpoints and/or chromosome segregation. These processes leading to sCNV are by their nature intrinsic features of cancer cells and occur in an undirected manner in terms of chromosome location and direction of change. Since generation of sCNV is ongoing and will lead to neutral, increased, or decreased fitness of the corresponding cell in its environment, different derivatives will have consequently different abilities to grow and survive, therefore leading to evolution of the tumor over time.