Cancer is caused by mutations in Genes. Cancer is mostly a disease for the aging due to an increased number of genetic mutations over time. When clonal proliferation occurs, a single cell with a mutation has an increase growth rate as well as a decreased death rate. With a faster accumulation of this specific mutated cell, it could become an early stage of a tumor. With more and more of the mutated cell, a normal to fully malignant cancer can develop.
There are different types of Gene Mutations in Cancer such as: alteration of progrowth and antigrowth signals, angiogenesis, and telomeres and immortality. For a cancer cell to become fully malignant the cell must be able to grow without needing external growth signals. Some cells stimulate their own growth with autocrine stimulation and some cancers increase their growth factor receptors. Many cancers have an activating mutation in their ras, or their intracellular signaling protein. This 'mutant ras' stimulates growth even when growth factors are lacking. The antigrowth signal must be inactivated in cancer as well as being able to grow without growth factors. Advanced cancers must overcome apoptosis by disabling the self-destructing mechanism. To maintain an advanced cancer or grow a small cancer, angiogenesis is needed. Angiogenesis is the development of blood vessels in order to deliver oxygen and nutrients. Telomeres and immortality is another component to gene mutation in cancer. Cancer cells somehow activate telomerase to restore and maintain there telomeres, protect their chromosomes, and sometimes develop the ability to divide repeatedly.
Oncogenes are mutant genes that in their normal non-mutant state direct synthesis of proteins that positively (accelerate) regulate proliferation. Tumor-suppressor genes encode proteins that are in their normal state negatively (put the brakes on) regulate proliferation. Mutations that create oncogenes are: point mutations, chromosome translocations, and chromosome amplification. A point mutation is the alteration of one or a few nucleotide base pairs. Chromosome translocations can activate oncogenes by either causing an excess and inappropriate production of a proliferation factor or by leading to production of novel proteins with growth-promoting properties. Chromosome amplification is the result of duplicating a small piece of a chromosome over and over again so that there are way too many copies.
When tumor suppressor genes, such as retinoblastoma (Rb) genes are inactivated, cell division is no longer inhibited and the cell can divide and can continue without any disruption. Point mutation can inactivate Rb on a cell's chromosome. When this happens the tumor suppressor will continue to be inactivated in newly made cells. The loss of heterozygosity is the loss of a chromosome region in a tumor and this unmasks mutations in recessive tumor suppressor genes. Gene silencing doesn't require mutations or changes in the DNA sequence, it is an important way to inactivate tumor suppressor gene expression in cancers. When taking mutations into account, the ways the genetic information can be compromised are: during each round of DNA synthesis, during each mitosis when chromosomes are segregated to daughter cells, and when external mutagens alter or disrupt DNA. When chromosome instability is ongoing in certain recessive traits malignant cells are increased due to the acceleration of the loss of tumor suppressor genes and the overexpression of oncogenes. Cancers that are inherited are due to the mutated cell being in the germ line, mutated somatic cells are not inherited. With the characterization of cancer-causing genes and other genetic factors, we can identify and help treat in earlier stages rather in the later stages.
By Meredith Hunt
Huether, S. , McCance, K. , Brashers, V. , & Rote, N. (2008). Understanding pathophysiology. (4 ed., pp. 228-235). St. Louis: Mosby Elsevier.