Evolution of the cancer genome英文文献资料.pdfVIP

Review Evolution of the cancer genome Ondrej Podlaha, Markus Riester, Subhajyoti De and Franziska Michor Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA Human tumors result from an evolutionary process op- bases for cancer initiation and progression? And are cancer- erating on somatic cells within tissues, whereby natural associated phenotypes gained via gradual accumulation of selection operates on the phenotypic variability gener- alterations or through punctuated, catastrophic events? ated by the accumulation of genetic, genomic and epi- Although the notion that cancer progression is an evolution- genetic alterations. This somatic evolution leads to ary process has been recognized for decades [4–6], this adaptations such as increased proliferative, angiogenic, framework of thinking has recently started to gain new and invasive phenotypes. In this review we outline how appreciation among cancer biologists and clinicians. Under- cancer genomes are beginning to be investigated from standing the forces that govern cancer initiation and lead to an evolutionary perspective. We describe recent prog- the acquisition of resistance to anti-cancer therapy repre- ress in the cataloging of somatic genetic and genomic sent very pressing issues in medical oncology. Here, we alterations, and investigate the contributions of germ- review recent progress in elucidating the evolution of cancer line as well as epigenetic factors to cancer genome cells on the genetic, genomic, and epigenetic levels, and evolution. Finally, we outline the challenges facing provide new