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Mutation and Cancer

The abnormal behaviors demonstrated by cancer cells are the result of a series of mutations in key regulatory genes. The cells become progressively more abnormal as more genes become damaged. Often, the genes that are in control of DNA repair become damaged themselves, rendering the cells even more susceptible to ever-increasing levels of genetic mayhem.

Below is an animation that demonstrates the relationship between chromosomes, genes and DNA.

Most cancers are thought to arise from a single mutant precursor cell. As that cell divides, the resulting 'daughter' cells may acquire different mutations and different behaviors over a period of time. Those cells that gain an advantage in division or resistance to cell death will tend to take over the population. In this way, the tumor cells are able to gain a wide range of capabilities that are not normally seen in the healthy version of the cell type represented. The changes in behavior seen in cancer cells are the focus of the Cancer Biology section of the site.

Mutations in key regulatory genes (tumor suppressors and proto-oncogenes) alter the behavior of cells and can potentially lead to the unregulated growth seen in cancer.

For almost all types of cancer studied to date, it seems as if the transition from a normal, healthy cell to a cancer cell is step-wise progression that requires genetic changes in several different oncogenes and tumor suppressors. This is one reason why cancer is much more prevalent in older individuals. In order to generate a cancer cell, a series of mutations must occur in the same cell. Since the likelihood of any gene becoming mutated is very low, it stands to reason that the chance of several different mutations occuring in the same cell is truly very unlikely. For this reason, the cells in a 70 year old body have had more time to accumulate the changes needed to form cancer cells but those in a child are much less likely to have acquired the requisite genetic changes. Of course, some children do get cancer but it is much more common in older individuals. The graph below shows colon cancer rates in the United States as a function of age. The graph was obtained from the National Cancer Institute. (1)

colon cancer as a function of age

By looking at the shape of curves like the ones shown above, it has been concluded that several genetic changes are required to create cells that become cancerous.

In the laboratory, researchers have been attempting to create tumor cells by altering or introducing key regulatory proteins. Several studies have attempted to define the minimal number of genetic changes needed to create a cancer cell, with intriguing results.(2)

In nature, mutations can accumulate in cells over time and if the 'right' group of genes are mutated, cancer can result.  A 2012 study showed that  bone marrow stem cells in a healthy individual accumulate many mutations as the person ages.  Just a few more changes to key genes can cause cancer.  The results imply that 'normal' cells and cancer cells may not be all that different in many cases.(3)

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Last Modified: 09/17/2012 Print Email Page
References for this page:
  1. Surveillance, Epidemioloy, and End Results (SEER) represented by National Cancer Institute [http://seer.cancer.gov]
  2. Hahn WC, Counter CM, Lundberg AS, Beijerbergen RL, Brooks MW, Weinberg RA. "Creation of human tumour cells with defined genetic elements." Nature 400: 464-468 [PUBMED]
  3. Welch JS, Ley TJ, Link DC, Westervelt P, Walter MJ, Graubert TA, DiPersio JF, Ding L, Mardis ER, Wilson RK et al. The origin and evolution of mutations in acute myeloid leukemia. Cell, July 20, 2012 [http://www.sciencedirect.com/science/article/pii/S0092867412007775] [PUBMED]
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