Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis

The evolution of colorectal cancer suggests the involvement of many genes. We performed insertional mutagenesis with the Sleeping Beauty (SB) transposon system in mice carrying germline or somatic Apc mutation. Analysis of common insertion sites (CISs) isolated from 446 tumors revealed many hundreds of candidate cancer drivers. Comparison to human datasets suggested that 234 CIS genes are also deregulated in human colorectal cancers. 183 CIS genes are candidate Wnt targets, and 20 are shown to be novel modifiers of canonical Wnt signaling. We also identified gene mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included members of the FGF signaling cascade. Some 70 genes showed pairwise co-occurrence clustering into 38 sub-networks that may regulate tumor development

Oncological Applications of Positron Emission Tomography with Fluorine-18 Fluorodeoxyglucose

Positron emission tomography (PET) is now primarily used in oncological indication owing to the successful application of fluorine-18 fluorodeoxyglucose (FDG) in an increasing number of clinical indications at different stages of diagnosis, and for staging and follow-up. This review first considers the biological characteristics of FDG and then discusses methodological considerations regarding its use. Clinical indications are considered, and the results achieved in respect of various organs and tumour types are reviewed in depth. The review concludes with a brief consideration of the ways in which clinical PET might be improved