CancerQuest | Inversions, Duplications, Deletions, and Aneuploidy

Inversions

In these alterations, segments of DNA are released from a chromosome and then re-inserted in the opposite orientation. As in the previous examples, this rearrangement can lead to abnormal gene expression, either by activating an oncogene or de-activating a tumor suppressor gene.

Duplications/Deletions

Through replication errors, a gene or group of genes may be copied more than one time within a chromosome. This is different from gene amplification in that the genes are not replicated outside the chromosome and they are only copied one extra time, not hundreds or thousands of times. Genes may also be lost due to failure of the replication process or other genetic damage.

Aneuploidy

A genetic change that involves the loss or gain of entire chromosomes. Due to problems in the cell division process, the replicated chromosomes may not separate into the daughter cells accurately. This can result in cells that have too many chromosomes or too few chromosomes. An example of a fairly common aneuploid condition that is unrelated to cancer is Down syndrome, in which there is an extra copy of chromosome 21 in all of the cells of the affected individual.

In the animation below, copies of two chromosomes are made but when the cell divides the chromosomes are not distributed evenly to the two cells that are formed (daughter cells). The result is that one of the cells has too many chromosomes and one does not have enough.

Cancer cells are very often aneuploid. Humans normally have 46 chromosomes in their cells, but cancer cells often have many more, sometimes greater than100. The presence of the extra chromosomes makes the cells unstable and severely disrupts the controls on cell division. There is currently an ongoing debate as to whether or not all cancers are aneuploid. Regardless of whether that is the case, it is clear that aneuploidy is a common feature of cancer cells.