| Abstract: |
The evolution of multicellular organisms requires symbiosis among cells, which cooperate to support organismal development and tissue homeostasis. These tasks require intercellular signaling and regulated cell proliferation and migration. Nevertheless, the program for these functions is encoded within the genome of each individual cell. Thus the maintenance of genome integrity requires surveillance, repair, and if necessary cell death to ensure that this program is not rewired to give rise to malignancy. Such rewiring requires multiple genetic changes, each of which happens at a low frequency under normal conditions. However, environmental factors (e.g., mutagenic chemicals and radiation) or intrinsic defects in genome integrity mechanisms (a “mutator” phenotype) can increase the probability of acquiring the necessary set of mutations. Indeed, considerable evidence indicates that most if not all tumors are much more genetically unstable than normal cells. While this instability provides an evolutionary advantage to cancer cells, it may also create novel liabilities that can be exploited therapeutically. Here we review the current state of knowledge about genetic alterations in cancer, including types and mechanisms of genomic instability and how they elicit oncogenesis. A revolution in chemistry emerged in nineteenth-century Germany as organic chemistry emerged in concert with increased availability of coal tar, a ready source of organic heterocycles. As a result, chemists were able to produce synthetic dyes for clothing that could be manufactured rapidly, in great quantity, and without the usual requirements for agricultural raw materials. Astute observers such as Walther Flemming noted that certain such dyes could stain vital stuctures in animal cells, visible by light microscopy. In particular, basophilic dyes labelled a chromatin. This revealed that cells, in an elaborate process, partitioned chromatin accurately into daughter cells. Flemming published his findings in 1882 and termed the division process mitosis (Figure 7.1) [1]. © Cambridge University Press 2015. |
