The Role of Aneuploidy in Cancer

The definition of aneuploidy is when the number of chromosomes found in a cell is either higher or lower than normal. In human cells, the correct number of chromosomes is 46. Anything more or less than this number would be considered to be an aneuploid cell. Aneuploidy is already known to cause a number of disorders and syndromes in humans that can range from very mild to severe. It is also thought to be the underlying cause of cancerous tumors as cells taken from the tissues of tumors have been found to always contain an abnormal number of chromosomes.

The theory of aneuploidy as the cause of cancer is not new to science. In 1891, German scientist David von Hansemann hypothesized that all cells from cancerous tissue would have an abnormal chromosome count after observing several samples of tissue taken  from epithilial cancers. Then, in 1914, the first theory of aneuploidy as the cause of cancer was published by German scientist Theodor Boveri. Boveri’s theory was based on experiments he made with fertilized sea urchin embryos. He noticed how abnormalities arose when the sea urchin eggs were fertilized with two sperm instead of one, which resulted in an embryo having three pairs (triploid) of chromosomes instead of the normal two pairs (diploid). This observation led to more experiments of how cells divide and the mechanisms necessary for normal mitosis and meiosis.

Boveri’s theory of aneuploidy as the cause of cancer was debated over and eventually put on the back burner when the theory of mutated genes, known as oncogenes and tumor-suppressant genes, became the new possible cause of cancer. Unfortunately, evidence of oncogenes as the sole trigger for cells to become cancerous has yet to be proved. In the late 1990s, the theory of aneuploidy as the cause of cancer was revisited.

In normal cell mitosis, specific check points are used to maintain the functions of division. The separation of the chromosomes into the new daughter cells is regulated by enzymes. When these enzymes are no longer functioning correctly, mistakes are made and chromosomes may be distributed unequally into the new cells resulting in aneuploidy. In most cases, cells with abnormal chromosome counts do not survive to further divide as there are other mechanisms at play that regulate abnormalities. In cancerous cells that have already divided numerous times, all normal check point regulation has been altered.

Enzymes that are no longer functioning correctly are usually the result of some sort of mutation to the gene that coded for the enzyme and its function. The cause of the mutation is most likely some sort of chemical that is known to have mutagenic properties. In an experiment involving mice, the chemical Bisphenol A, also known as BPA, was found to increase the rate of meitotic aneuploidy. Bisphenol A is a chemical found in plastic water bottles and other food containers. While this study did show a significant increase of aneuploidy in rats caused by this chemical, human studies are still underway. Other mutagenic chemicals, also known as carcinogens, such as the compounds found in cigarette smoke are also believed to cause the types of mutations that would lead to aneuploidy.

A cell with an abnormal amount of chromosomes will also have more than the usual number of genes. A normal diploid cell will perform necessary functions with out any problems because it is receiving the correct signals from the enzymes and other proteins produced from the normal genetic expression. An aneuploid cell will not have normal gene expression as it is receiving a huge amount of signalling or an absence of signalling. This is why cancer cells do not behave the same way as normal cells do. Excessive amounts of genetic material create a huge mess of confusion to the cell which could be compared to having over one hundred people all shouting different instructions to one person on how to perform their job.

The theory of aneuploidy as the cause of abnormalities that could possibly lead to cancer has already been found to be valid with other types of syndromes that are caused by aneuploidy. Down syndrome, Emanual syndrome, trisomy 13, and Turner syndrome are all caused by the addition of a single chromosome, or piece of a chromosome, and are all cases of aneuploidy but at a much smaller scale. By comparison, cancer cells have been found with 60-90 chromosomes per cell. A key difference between the syndromes listed previously and cancer cells is where the aneuploidy occurred. The occurrence of aneuploidy in germ cells (egg or sperm) will result in the syndromes, while aneuploidy in somatic cells (tissues of organs) will result in possible cancer. None the less, cells with any degree of aneuploidy that are allowed to survive will result in some sort of abnormality.

As with cancer in general, the underlying causes of aneuploidy are still yet to be discovered. There is definitely strong evidence at hand that connects aneuploidy to the formation of cancer. This is just one of the many pieces of the puzzle that makes up how and why cancer even exists.