This proposal is to request support for a Keystone Symposia meeting entitled """"""""Cancer Genomics and Epigenomics"""""""", organized by Andrew P. Feinberg, Greg J. Hannon and Rolf Ohlsson, which will be held in Taos, New Mexico from February 19 - 24, 2008. In the """"""""post-genome"""""""" era, in which the human DNA sequence is available, as are those of many animal models, cancer genetics is being transformed both by the access to this sequence and by the technology that the genome project facilitated. It is now clear that many genetic changes occur in tumors, including mutations and copy number changes, as well as an even larger number of epigenetic alterations, such as altered DNA methylation, chromatin modification, and loss of genomic imprinting. High-throughput genomic and epigenomic approaches are now available, but are also being developed to assess the scope of these genomic/epigenomic changes. There is also a deeper evolution of our understanding that the genome and epigenome may be intrinsically disrupted in tumors, for example by palindrome formation and whole-band methylation. These advances raise several major questions, including: Which genetic and epigenetic changes play a causal role in tumor initiation and progression? What is the genetic and epigenetic basis of cancer predisposition? Is there large scale disruption of the cancer genome and epigenome and how does this arise? And how can we exploit advances in cancer genomics and epigenomics? What are the cutting edge technologies that will advance the sensitivity of detection of subpopulations such as cancer stem cells? This symposium will explore the technological developments, large scale alterations, and gene-specific changes emerging in the genome-wide approach to cancer, as well as the implications of these discoveries for cancer prevention and therapy. ? ? ? ?
