Mutations : Germline mutations and somatic mutations

Mutations defined as changes in the sequence of the bases, can occur by a number of means: for example, single base substitutions that might result from errors during DNA replication (copying of the DNA prior to cell division; see below), or deletion of larger pieces of a chromosome or translocation events (swapping pieces from one chromosome to another).

It is also important to note that mutations can be grouped into two general categories, germline and somatic.

Germline mutations are those that we inherit from our parents and will pass on to our children, while somatic mutations are those that occur during our lifetime and are not passed on to our descendants. Most mutations have no effect on our health and lifespan because they result in changes to DNA base sequences that do not alter the coded genetic information.

However, those mutations that make changes to the genetic information such that cells no longer can control their growth are the hallmark of cancer. The discovery of the structure of DNA in 1953 by James Watson and Francis Crick initiated a rapid increase in the study of how the information encoded in the double-helical fibers of DNA was copied and passed from generation to generation. It has been estimated that the human genome carries approximately 35,000 sequences whose codes are read to produce protein molecules with specific metabolic functions.

In cells that are growing and dividing, and even in those cells in a resting phase, mutations occur at an alarmingly high rate, both from normal cellular processes (e.g., copying of the DNA strands prior to cell division) and from exposure to environmental or chemical carcinogens [e.g., the ultraviolet rays in sunlight or especially cigarette smoke (at least 40 different carcinogens are found in a typical cigarette)]. However, all cells use remarkably effective strategies to either avoid mutations or to repair them when they occur.

Cell signaling

Cells communicate and respond to the extracellular environment through a process designated signal transduction. Signal molecules bind to transmembrane receptors that span the cell membrane. The interaction of signal molecules with components of receptors located outside the cell modifies the intracellular components of the receptors. An environmental signal is thereby transduced into a cascade of regulatory steps that control genes which control cell proliferation and specialized properties of cells.

In some signaling pathways, scaffold proteins assemble signaling molecules into complexes for the initial passage of information from the transmembrane receptor to relay and adaptor proteins. Subsequent steps in the signaling process amplify and integrate signals. A chain of intracellular signaling proteins processes regulatory information through the cytoplasm and into the cell nucleus to activate or suppress genes. In other signaling pathways the regulatory cascades are abbreviated. The transduction of regulatory information from the intracellular component of the transmembrane receptor is more direct, circumventing intermediary steps in information transfer. At an early stage in the signaling process a signaling protein enters the nucleus and interacts directly with genes to modify expression.

Many cancer cells exhibit defects in one or more steps of signaling cascades that alter control of
cell growth, specialized cell properties, cell–cell communication, cell motility, and cell adhesion. The components of signaling pathways that are modified in tumor cells are targets for treatments that are effective and specific.

CANCER CELL BIOLOGY

Cells are the units of life. Normal cells act on each other to control their growth and other properties in balance with the entire organism. They are closely regulated by a variety of genetic and biochemical processes. For example, biological feedbacks act in much the same way that a thermostat controls heat production by a furnace. Cancer is a disease of ‘‘outlaw’’ cells, cells that have lost their normal relationship to the whole organism. A tumor originates when single normal cells mutate and develop into cancer cells, termed transformed cells. Mutations produce defects in their cellular regulatory mechanisms, changing their biochemistry and biology so that they differ from normal cells in structure and functioning and grow at the wrong times and in the wrong places.

Briefly, each cell is surrounded by a membrane that separates it from its surroundings, which include other cells, nutrients, and molecules that regulate growth and other functions. Within the cell is a fluid, cytoplasm, containing proteins and structures, including mitochondria (the source of energy for a cell , that produce chemical energy and the machinery (ribosomes) that synthesizes proteins. The nucleus, which contains the genetic material, sits in the middle of the cell. Location within a cell can determine a molecule’s possible biochemical interactions and effects. Cells of cancers develop into disorganized arrangements, and their nuclear shapes are abnormal, properties that are scrutinized carefully during diagnosis and are used to classify the stage of a cancer.