A new study shows for the first time how a jumping gene can trigger colorectal cancer. Scientists have known about "jumping genes" - pieces of DNA that can move from one part of the genome to another - since the 1940s.
During that decade, geneticist and Nobel laureate Barbara McClintock discovered them while studying maize plants.
More recently, scientists have shown that jumping genes - more formally known as transposable elements or transposons - are surprisingly prevalent in human genomes and are active in many cancers.
Now, for the first time, in a paper published in the journal Genome Research, researchers show conclusively that one of these jumping genes plays a key role in triggering colorectal cancer.
For their study, senior author Scott E. Devine, associate professor of medicine at the University of Maryland School of Medicine in Baltimore, and colleagues focused on a transposon called L1.
Until about 25 years ago, scientists thought L1 had no effect. However, since then, studies have shown it is active in the brain and body and in diseases, including some types of hemophilia and many cancers.
Triggering cancer by mutating genes that suppress tumors
In 2010, Prof. Devine and colleagues reported how they developed new technologies that allowed them to detect insertions of transposons, including L1, and showed how they were abundant in human populations and very active in lung cancer genomes.
Despite these discoveries, no study had found a clear link between L1 and cancer. So, the team decided to investigate the idea that perhaps L1 triggers cancer by causing mutations in genes that suppress tumors.
After screening tumors from 10 patients, the researchers found evidence of L1 insertions into the APC gene in the case of one patient. These insertions were not found in healthy tissue.
In their paper, the researchers report that one new L1 insertion inactivates the APC gene. Prof. Devine says such gene silencing allows tumors to grow unhindered.
He and his colleagues describe the new insertion as a "hot L1 source element on Chromosome 17 of the patient's genome" that evaded suppression in normal tissue and thereby triggered colorectal cancer by mutating the APC gene.
The researchers note that the new L1 insertion also pairs up with a mutation in the patient's second copy of the APC gene, and thus acts via a "two-hit" pathway to trigger cancer.
"This is really a new way to understand how tumors grow. We think it could explain a lot about the mutation process that underlies at least some cancers."
Prof. Scott E. Devine
Prof. Devine says the patient whose tumor led to the discovery also had a strong family history of cancer, leading them to suggest perhaps certain groups or families are more prone to cancers with active L1 insertions.
While this study shows how transposons can promote disease, it is important to note they likely also help normal cell functions, since they make up a large portion of our DNA.
In fact, more than half of our genome comprises jumping genes like L1, and their variability is probably an important element in deciding our individual genetic makeup.