Genetics of cancer
CANCER: A GENETIC DISEASE:
Mutations in genes that control cell growth and division are responsible for cancer.
Cancers arise when critical genes are mutated. These mutations can cause biochemical processes to go away and lead to the unregulated proliferation of cells. ‘Without regulation, cancer cells divide ceaselessly, piling up on top of each other to form tumors. When cells detach from a tumor and invade the surrounding tissues, the tumor is malignant.
The Many Forms of Cancer
Cancer is not a single disease, but rather a group of diseases. Cancers can originate in many different tissues of the body. Some grow aggressively, others more slowly.
Cell Cycle
•The cell cycle consists of periods of growth, DNA synthesis, and division. The length of this cycle and the duration of each of its components are controlled by external and internal chemical signals. The transition from each phase of the cycle requires the integration of specific chemical signals and precise responses to these signals. If the signals are incorrectly sensed or if the cell is not properly prepared to respond, the cell could become cancerous.
•The current view of cell-cycle control is that transitions between different phases of the cycle (G1, S, G2, and M) are regulated at “checkpoints.” A checkpoint is a mechanism that halts progression through the cycle until a critical process such as DNA synthesis is completed, or until damaged DNA is repaired. Two types of proteins are known to play especially critical roles: the cyclins and the cyclin dependent kinases, (CDKs). Complexes formed between the cyclins and the CDKs cause the cell cycle to progress.
•The cyclins enable the CDKs to carry out their function by forming cyclin/CDK complexes. When the cyclins are absent, these complexes cannot form, and the CDKs are inactive. Cell cycling therefore requires the alternate formation and degradation of cyclin/CDK complexes.
•One of the most important cell-cycle checkpoints, called START is in mid-G1 . The cell receives both external and internal signals at this checkpoint to determine when it is appropriate to move into the S phase. This checkpoint is regulated by D-type cyclins in conjunction with CDK4. If a cell is driven past the START checkpoint by the cyclin D/CDK4 complex, it becomes committed to another round of DNA replication. Inhibitory proteins with the capability of sensing problems in the late G1 phase, such as low levels of nutrients or DNA damage, can put a brake on the cyclin/CDK complex and prevent the cell from entering the S phase.
•In tumor cells, checkpoints in the cell cycle are typically deregulated. This deregulation is due to genetic defects in the machinery that alternately raise and lower the abundance of the cydin/CDK complexes. For example, the genes encoding the cyclins or the CDKs may be mutated, or the genes encoding the proteins that respond to specific cyclin/CDK complexes or that regulate the abundance of these complexes may be mutated. Many different types of genetic defects can deregulate the cell cycle, with the ultimate consequence that the cells may become cancerous.
•Cells in which the START checkpoint is dysfunctional are especially prone to become cancerous.
Cancer and Programmed Cell Death
•Cell death is part of the normal developmental program in this animal—and in others too, for we know, for example, that during the development of the hands and feet of many vertebrates, the cells that lie between the developing digits must die; if they do not, the digits remain fused. Programmed cell death is therefore a fundamental and widespread phenomenon among animals. If a cell with an abnormal ability to replicate is killed, it cannot multiply to form a potentially dangerous tumor. Thus, programmed cell death is an important check against renegade cells that could otherwise proliferate uncontrollably in an organism.-
A Genetic Basis for Cancer
•First: When cancer cells are grown in culture, their descendants are all cancerous indicating that cancer has a genetic basis. Second, it was known that certain types of viruses can induce the formation of tumors in experimental animals. The induction of cancer by viruses implies that the proteins encoded by viral genes are involved in the production of the cancer state. Third, it was known that cancer can be induced by agents capable of causing mutations. Mutagenic chemicals and ionizing radiation had been shown to induce tumors in experimental animals. Fourth, it was known that certain types of cancer tend to run in families. In particular, susceptibility to retinoblastoma, rare cancer of the eye, and susceptibility to some forms of colon cancer appeared to be inherited as simple dominant conditions albeit with incomplete penetrance and variable expressivity cause susceptibility to these special types of cancer.
•Finally, it was known that certain types of white blood cell cancers (leukemia and lymphomas) are associated with particular chromosomal aberrations. Cancer researchers have identified two broad classes of genes that, when mutated, can contribute to the development of a cancer state. In one of these classes, mutant genes actively promote cell division; in the other class, mutant genes fail to repress cell division.
