In:
eLife, eLife Sciences Publications, Ltd, Vol. 4 ( 2015-09-16)
Abstract:
Prostate cancer is the most common type of cancer in men in the UK and USA. Cancers develop when cells in the body acquire genetic mutations that allow the cells to grow rapidly and form a mass known as a tumor. Prostate cancer cells from different individuals can carry different genetic mutations, which affects whether the disease progresses and how the tumors respond to medical treatments. This genetic variety arises in cancer cells partly from a phenomenon known as genomic instability, in which DNA mutations accumulate due to defects in DNA repair. Genetic studies of biopsies taken from human prostate cancers have shown that genomic instability causes chromosomes—the structures in which the cell's DNA is organized—to break and then be stuck back together haphazardly. As a result, fragments of chromosomes can end up in the wrong position, be duplicated, or be lost altogether. All of these mutations could spur on the growth of the tumor. However, it is currently not clear why some prostate cancers are more genomically unstable than others, or what exactly causes this instability. Boysen, Barbieri et al. studied prostate cancer cells taken from patients before they started medical treatment. The experiments show that the cancer cells with high levels of genomic instability also often had mutations in a gene that encodes a protein called SPOP. These mutations occur in about 10 percent of men with prostate cancer and appear early in the development of the tumors. Next, they studied the SPOP protein in zebrafish (which is nearly identical to human SPOP), as well as in mouse and human cells. The experiments show that SPOP normally helps the cell to accurately repair DNA that has been damaged. Mutations in SPOP change the DNA repair process, which lead to genomic instability by increasing the likelihood that broken chromosomes will be stuck back together incorrectly. Further experiments tested drugs known as PARP inhibitors on mouse and human prostate cancer cells. The drugs, which have been recently tested successfully in patients with prostate cancer, block a different method of DNA repair that operates separately to the one that involves SPOP. When both of these pathways were inactivated—one by the SPOP mutation, the other by the drug—the cancer cells died more quickly. Therefore, men that are diagnosed with types of prostate cancer in which the gene that encodes SPOP is mutated might benefit from treatment with PARP inhibitors or other therapies that affect DNA repair.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.09207.001
DOI:
10.7554/eLife.09207.002
DOI:
10.7554/eLife.09207.003
DOI:
10.7554/eLife.09207.004
DOI:
10.7554/eLife.09207.005
DOI:
10.7554/eLife.09207.006
DOI:
10.7554/eLife.09207.007
DOI:
10.7554/eLife.09207.008
DOI:
10.7554/eLife.09207.009
DOI:
10.7554/eLife.09207.010
DOI:
10.7554/eLife.09207.011
DOI:
10.7554/eLife.09207.012
DOI:
10.7554/eLife.09207.013
DOI:
10.7554/eLife.09207.014
DOI:
10.7554/eLife.09207.015
DOI:
10.7554/eLife.09207.016
DOI:
10.7554/eLife.09207.017
DOI:
10.7554/eLife.09207.018
DOI:
10.7554/eLife.09207.019
DOI:
10.7554/eLife.09207.020
DOI:
10.7554/eLife.09207.021
DOI:
10.7554/eLife.09207.022
DOI:
10.7554/eLife.09207.023
DOI:
10.7554/eLife.09207.024
DOI:
10.7554/eLife.09207.027
DOI:
10.7554/eLife.09207.028
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2015
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2687154-3
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