Incollection,
Genomic Instabilities, DNA copy number changes and Cancer
Abstract Book of the XXIII IUPAP International Conference on Statistical Physics, Genova, Italy, (9-13 July 2007)
Abstract
The focus of cancer research has shifted during the past decade from data acquisition and phenomenology towards a logical science that aims at understanding initiation and progression of the disease in terms of a small number of underlying simple principles. Indeed, the basic hallmarks of cancer, i.e. the minimal set of high-level regulatory networks and circuits that must break down in order to transform a normal cell to a malignant one, have been identified. A relatively simple theory of the causes and basic mechanisms that drive tumorigenesis is based on the concept of alterations (mutations, translocations, deletions etc) that occur on the single gene level. These genetic changes either generate oncogenes, proteins whose abnormal activity causes cancer, or induce loss of function of tumor suppressors proteins that arrest the cancerous process in normal cells. Mutations in many oncogenes and tumor suppressors have indeed been identified in all cancers. In addition to these single-gene alterations, most tumors were found to exhibit very large-scale genomic instabilities: deletions of amplifications of entire chromosomal regions!
The classical model which views single-gene alterations as causative, and the chromosomal instabilities mainly as a side effect has been seriously challenged; claims that view these instabilities as the major cause of cancer are forcefully made.
I will review recent work that studies the extent of 'chromosomal chaos' observed in several kinds of cancer, and describe the role they appear to play in cancer initiation and progression.
