Amplified genes correlate with cancer survival
A new group of genes that are present in several copies in cancer cells were found to correlate with reduced cell growth and to predict patient survival. Thereby the genes represent potential new targets for anti-cancer therapy. This is shown in a recent international paper in Nature Communications, where IGP researcher Verónica Rendo is first author.
Cancer is considered as a genetic disease where changes in the genome leads to uncontrolled cell growth. A common genetic alteration in cancer cells is copy number alterations where sections of the DNA are amplified and occur in more copies than normal. As a result, genes in an amplified DNA section, which can include hundreds of genes, will also be present in several copies. More copies usually mean increased gene expression, which can affect cancer growth.
However, copy number alterations do not always correlate with affected genes’ expression levels, suggesting that the cancer cells cannot tolerate the presence of additional copies of certain genes. In the present study, the researchers have identified a large number of such genes that are “toxic” to cancer cells, when they are present in several copies.
“Researchers often focus on the genes that when expressed at these high levels contribute to disease progression, often termed oncogenes. Instead, we have studied the many others genes that also become amplified and that traditionally are disregarded. Our results show that the amplification and expression status of some of these genes can even predict patient survival and response to certain treatments,” says Verónica Rendo, first author of the article.
Out of the hundred or so identified genes, the researchers chose one to study in more detail. This gene, RBM14, encodes a protein that is involved in the repair of DNA damage, which is important in cancer cells that are dividing very actively.
“We examined how an increased copy number of RBM14 affected cultivated lung and breast cancer cells and found that it resulted in a higher rate of aberrant cell divisions and a reduced cell proliferation. This suggests a mechanism by which RBN14 overexpression leads to cell death. We also found a positive correlation between RBM14 copy number and survival in irradiation treated colorectal cancer patients, says Verónica Rendo.
The researchers conclude that the genes they have identified as cellular liabilities when overexpressed could be considered as potential new targets for anti-cancer therapy. There is therefore a clinical motivation to look into these further.