Scientists have discovered hundreds of genes that could potentially promote cancerA new study reveals.
Cancer is usually caused by some kind of change to the genetic code that impedes the ability of cells to manage their growth. Tailored treatments that target these impediments can stop tumors from spreading uncontrollably.
To date, over 600 genes are known to cause tumors when their sequences are compromised by mutations, but there are other ways in which cancer can develop in the pathway between the transcription of a gene and its final product.
While most previous research in this field has looked at abnormalities inherent in the DNA itself, this study looks at abnormalities that arise when instructions from DNA are transmitted to other parts of the body.
Using a carefully constructed algorithm, researchers at the Barcelona Institute of Science and Technology (BIST) in Spain have Exon: The part of a gene sequence that is translated directly into a protein.
Non-coding parts of genes, called introns, are normally removed when the gene’s DNA is transcribed into the RNA version. SplicingCancer cells can disrupt splicing and produce mutated proteins from normal, unmutated protein genes.
Using a carefully constructed algorithm, the team identified 813 genes that, when combined, could drive cancer growth.
This broad new category expands the list of cancer-promoting genes, building on an existing list of 626 genes known to cause tumors when mutated.The most widely used cancer mutation databases already contained only about one-tenth of the “splice” classes that record genes that drive cancer growth. Through mutation.
“We believe that when we consider non-mutational mechanisms such as splicing, the number of potential genetic targets for controlling cancer may double.” say Miquel Anglada-Girotto, a biologist at BIST.
“These are not typical cancer genes, but rather represent an entirely new class of potential cancer-inducing factors that can be targeted alone or in synergy with existing strategies.”
The researchers’ algorithm, which they called “Spotter,” was able to comb through vast amounts of genetic data and identify splicing events that could increase the chances of cancer growing. In small-scale lab tests on tissue samples, targeting these exons actually suppressed the growth of cancer in the samples.
“Not only can Spotter identify potential cancer driver exons and trace them back to genes, it can also rank which exons are more important than others in a given cancer sample.” say Anglada Girotto.
The usefulness of identifying these exons didn’t stop there: Further analysis, combining data from this study with a database of drug treatment outcomes, showed that the splicing variants could help predict how different patients might respond differently to the same drug.
While there’s still a lot of work to be done before we can routinely highlight and target exons within genes, this study shows it’s likely achievable — and the more cancer-fighting weapons we have available, the better.
“This is very exciting new ground to explore.” say Anglada Girotto.
This study Nature Communications.
