We identified genomic and network properties of approximately 600 genes mutated in different cancer types. These genes tend not to duplicate but, unlike most human singletons, they encode central hubs of highly interconnected modules within the protein-protein interaction network (PIN). We find that cancer genes are fragile components of the human gene repertoire, sensitive to dosage modification. Furthermore, other nodes of the human PIN with similar properties are rare and probably enriched in candidate cancer genes.