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CIC encodes a transcriptional repressor and MAPK signalling effector that is inactivated by loss-of-function mutations in several cancer types, consistent with a role as a tumour suppressor. Here, we used bioinformatic, genomic, and proteomic approaches to investigate CIC’s interaction networks. We observed both previously identified and novel candidate interactions between CIC and SWI/SNF complex members, as well as novel interactions between CIC and cell cycle regulators and RNA processing factors. We found that CIC loss is associated with an increased frequency of mitotic defects in human cell lines and an in vivo mouse model and with dysregulated expression of mitotic regulators. We also observed aberrant splicing in CIC-deficient cell lines, predominantly at 3′ and 5′ untranslated regions of genes, including genes involved in MAPK signalling, DNA repair, and cell cycle regulation. Our study thus characterises the complexity of CIC’s functional network and describes the effect of its loss on cell cycle regulation, mitotic integrity, and transcriptional splicing, thereby expanding our understanding of CIC’s potential roles in cancer. In addition, our work exemplifies how multi-omic, network-based analyses can be used to uncover novel insights into the interconnected functions of pleiotropic genes/proteins across cellular contexts.

Next-generation DNA sequencing devices have revolutionized cancer genomics by bringing whole genome resequencing of patients' tumours within practical and economic reach. We present an overview of the techniques involved and review early results from the resequencing of cancer genomes. The possible impacts of whole-genome and trancriptome resequencing in clinical cancer research and the practice of pathology are discussed.

Genetic approaches to validating G protein-coupled receptors (GPCRs) have proven to be a powerful research tool, especially knockout studies in rodents. To date, data related to in vivo function have been published on approximately half of the human rhodopsin-like family-1 GPCRs, which can be attributed to the use of mouse knockouts. It is likely that many currently unknown yet important therapeutic mechanisms will be uncovered through knockout screens in mice. One such recent discovery is the elucidation of the in vivo function of the GPCR GPR54 through mouse genetics, and its subsequent validation in human populations. Although previously unsuspected, GPR54 has been found to be a master-regulator of the hypothalamic-pituitary-gonadal axis.