MUTATIONS AND CELL DEFENSES

INTRODUCTION
The information required for the development and growth of an organism is encoded in its deoxyribonucleic acid (DNA), the genetic material. In human cells, the entire DNA content, or genome, is packaged in 46 chromosomes that reside in the cell’s nucleus. Because this information is critically important for all biological processes occurring during the lifetime of an organism, evolution has resulted in many and various means by which a cell can either avoid damage to this information, or repair damage once it has occurred.

DNA is a double-strandedhelical ribbon, with each strand consisting of a continuous sequence of bases. Bases can be considered as the letters of words that are strung together to make up the information code. Remarkably, only four bases—adenine, guanine, cytosine, and thymine (A, G, C, and T)—are required to generate the amazingly diverse information encoded in the human genome, and it is the varying, ordered sequence of these bases that creates all the different bits of information along the DNA strand. For the purposes of our discussion in this chapter, remember that genetic information is decoded by the following general path: DNA codes for ribonucleic (RNA), acid which in turn codes for protein molecules, whose amino acid sequence derives from the DNA sequence. Although this is an oversimplification of the complex information contained within DNA, it suffices for our appreciation of how changes in the DNA sequence (mutations) may adversely effect cellular function.

General and tumor-type specific modifications

General and tumor-type specific modifications in nuclear organization are long-standing indications of cancer. Many cancers have alterations in the number and composition of nucleoli , the focal sites within the cell nucleus for ribosomal gene expression that supports protein synthesis. Chromosomal rearrangements are prevalent in cancer. Modifications in plasma membrane–associated receptors modify responses of the tumor cell to growth factors. Changes in integrins, molecules that mediate communication between the extracellular environment and the cytoplasm within a cancer cell, influence the transmission of information .

Cancer-related alterations occur in the exchange of signals between the cell nucleus and cytoplasm, which are critical for control of cell regulatory machinery. These changes provide insight into cellular and molecular parameters of cancer that facilitate tumor diagnosis and are targets for therapy. Effects of mutation that are found in most cancer cells are failures of molecular mechanisms that limit growth and differentiation into specialized cells, causing their death (apoptosis), their movement out of the tumor (metastasis), and the activation of a blood supply, which is required to feed the tumor (angiogenesis).