Changes in gene-gene interactions associated with cancer onset and progression are largely independent of changes in gene expression.

Recent findings indicate that changes underlying cancer onset and progression are not only attributable to changes in DNA structure and expression of individual genes but to changes in interactions among these genes as well. We examined co-expression changes in gene-network structure occurring during the onset and progression of nine different cancer types. Network complexity is generally reduced in the transition from normal precursor tissues to corresponding primary tumors. Cross-tissue cancer network similarity generally increases in early-stage cancers followed by a subsequent loss in cross-tissue cancer similarity as tumors reacquire cancer-specific network complexity. Gene-gene connections remaining stable through cancer development are enriched for "housekeeping" gene functions, whereas newly acquired interactions are associated with established cancer-promoting functions. Surprisingly, >90% of changes in gene-gene network interactions in cancers are not associated with changes in the expression of network genes relative to normal precursor tissues.