INTRODUCTION e unstable character of most cancers, as reected by the high levels of genomic, cytogenetic, and epigenetic variation, seems an almost universal feature of tumorigenesis. Such cellular disorder is particularly well illustrated by the presence of high levels of aneuploidy: multiple losses and gains of parts or even entire chromosomes can be seen, together with many chromosome rearrangements (Lengauer et al., 1998). It has been properly described as a “gallery of horrors” and such a disorder opens interesting, and I believe largely unanswered questions concerning the nature of cancer itself. e evolutionary dynamics of tumors is thus characterized by selection processes in parallel with unusual levels of genetic variation (Loeb, 1991) more consistent with what we would expect from unicellular systems (Cairns, 1997). Increased genetic instability has been suggested as an adaptive trait of microbial species. When facing high
CONTENTS Introduction 67 Mean Field Model 70 Digital Genome Model 75 Progression Paths as Complex Networks 81 Discussion 83 References 85
levels of environmental stress, those mechanisms controlling the accurate replication of DNA might be overcome and checkpoints ignored. is is less reasonable in the tissue context, where cooperation among cells and a control of tissue and organ size is an essential part of global homeostasis. Failures in properly replicating the genome face multiple internal controls that force the system to stop dividing or even to die.