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A cell that degenerates into a tumor cell does usually not acquire all these properties at once, but its daughter cells are selected to build them. This process is called cellular evolution. A first step in the development of a tumor cell is usually a small change in the DNA, often a point mutation, which leads, among other things, to a genetic instability of the cell. The instability increases to a point where the cell loses whole chromosomes, or has double ones. Also, the DNA methylation pattern of the cell changes, activating and deactivating genes more or less at random. Cells that divide at a high rate, such as stem cells, show a higher risk of becoming tumor cells than those which divide less or not at all, for example neurons. If the initial tumor cell (or group of tumor cells) is not removed by the immune system, it will develop into cancer.

In cellular model systems, cells are exposed to carcinogenic influences (chemicals, radiation). In these systems, the first signs of a cell developing into a tumor cell are:

  • Immortality. The usual number of cell divisions for a mammalian cell is 50-60 (cell senescence), then it ceases to divide. Tumor cells keep dividing forever.
  • Altered morphology.
  • Building of cellular clusters (Foci).
  • Loss of contact inhibition.
  • Low or no need for growth factors.

Items 2-4 (above) can sometimes be traced to mutations in genes that result in a disruption of cell adhesion. Some cell adhesion proteins are oncogenes.

For most of the cancers, it cannot be told which event was the initial cause. However, with molecular biology, it is possible to characterize the mutations within a tumor, and to a certain extent predict its behavior. For example, about half of the tumors are deficient in the tumor suppressor gene p53, also known as "the guardian of the genome". This is associated with poor prospects for the patient, since those tumor cells are unlikely to go into apoptosis (programmed cell death) after they are damaged by therapy. There are more mutations that make a tumor more malignant. Telomerase mutations enable a tumor cell to divide indefinitely. Other mutations enable the tumor to grow new blood vessels to feed it, or to detach from the surrounding tissue, spreading to other parts of the body.