Cancer

The body consists of many different organs, which in turn are composed of several different types of tissues. There are three major categories of tissue-related tumor types: carcinoma, sarcoma, and leukemia/lymphoma. There are also other specialized tumor categories, such as those of the central nervous system (e.g., brain tumors).

Carcinoma.

This is the largest category, containing about 90 percent of all cancers, and it consists of neoplasms derived from epithelial cells. Epithelial cells make up the outer layers of the skin. They also line the inner structures of organs such as the lungs, intestines and testes, as well as complex tissue such as the breast.

Sarcoma.

These are solid tumors derived from all connective tissues except the bloodforming tissues (these are the leukemias and lymphomas). These tumors account for about 2 percent of all cancers. They occur in such tissues as muscle, bone, and cartilage.

Leukemia and Lymphoma.

This group contains about 8 percent of all cancers, including blood cancers that originate from the marrow (leukemias) and from the lymphatic system (lymphomas). This group also includes other nonsolid tumors of the bone marrow and lymphatic system, such as myeloma, which affects plasma cells—a type of white blood cell found in the marrow and in other tissues.

Solid tumors are firm masses that develop from a neoplasm's originating organ, such as the brain, esophagus, kidney, liver, lung, ovary, pancreas, prostate, or testis. Tumors of the blood-forming tissues and lymphatic systems are not solid and tend to remain free and circulating even when malignant. Some of the common forms of cancer are listed in the table above.

Oncogenes.

These genes are involved in signal transduction, and some are involved in the various phases of the cell cycle. Mutations in cell-cycle regulation or signal transduction can "push" the cell into dividing rapidly and without regard to its surroundings. Over 100 oncogenes have been identified so far. They include genes such as ABL1 (Abelson murine strain leukemia viral homolog) and EGFR (Epidermal Growth Factor Receptor).

Tumor Suppressor Genes.

These genes inhibit cell division, working in a manner opposite to that of the oncogenes. Surrounding cells secrete growth-inhibitory signals that help prevent proliferation. These growth-inhibitory signals work in conjunction with tumor suppressor genes. If a tumor suppressor gene is mutated, proliferating cells can ignore these inhibitory messages. This group includes the genes p53, BRCA1, and BRCA2.

DNA Repair Genes.

These are the genes that provide the cell with the ability to sense and correct damage to the DNA. Damage to the DNA can be caused by radiation, chemicals, ultraviolet light, or errors in transcription. If these errors are not corrected, they accumulate in the genome and can Inheritance of a mutated retinoblastoma gene (Rb*) greatly increases the likelihood of developing the disease. quickly increase the chance that a cell will become cancerous. Repair genes include those in the DNA-ligase and excision-repair gene families.

Genes Involved in Cell Mortality.

A normal cell can only undergo about forty divisions, after which it dies or enters senescence. If a tumor had this limitation it would be very limited in its size, as it would reach its forty divisions relatively quickly. This process is controlled by the enzyme telomerase, which maintains the telomeres (repetitive DNA sequences at the ends of chromosomes that shorten after each round of DNA replication, until they reach a length that causes the cell to die) by not allowing them to shorten. Some cancer cells become immortal as a result of mutations in the telomerase gene, causing the telomeres to be extended indefinitely, allowing the cell to continue dividing without limit. Other mutations affect the process of apoptosis.

Cancer does not usually arise by a single event. Instead, two or more "hits" are needed to convert a well-regulated cell to a cancer cell. This is the case because each cell contains two copies of each gene, one inherited from each parent. Most cancer-causing mutations cause a loss of function in the mutated gene. Often, having only one functional copy is enough to prevent disease. Thus, two mutations are needed.

This can be illustrated by looking at retinoblastoma, a common cancer of the retina. The affected gene (called the retinoblastoma gene) is a tumor suppressor. Spontaneous mutations are rare, but since there are many millions of cells in the retina, several will develop the appropriate gene mutation over the course of a lifetime. It would be very unlikely, though, for a single cell to develop two spontaneous mutations (at least in the absence of prolonged exposure to carcinogens), and thus spontaneous retinoblastoma is very rare.

If, however, a person inherits one copy of an already-mutated gene from one parent, every cell in the eye starts life with one "hit." The chances are very high that several cells will suffer another hit sometime during their life, and so the chances are very high that the person will develop retinoblastoma. Since inheriting a single copy of the mutated gene is so likely to lead to the disease, the gene is said to show a dominant inheritance pattern.