Cancer Jumping Genes

Remember the Mexican Jumping Beans when we were young? I just saw them again recently while working in Mexico. You hold them in your hand and the heat from your body makes them jump around. Its a strange thing but there is even stranger things than that.

 Jumping gene can trigger colorectal cancer.

There is a new study that shows for the first time how a jumping gene can trigger colorectal cancer. The scientists have known about jumping genes, pieces of DNA that can move from one part of the genome to another, since the 1940’s. Nobel laureate and geneticist Barbara McClintock discovered them while studying maize plants. Recently they have shown the jumping genes are surprisingly prevalent in human genomes and are active in many cancers. Jumping genes are also known as transposable elements or transposons.

Published in the journal, Genome Research, researchers have shown for the first time conclusively that one of these jumping genes plays a key role in triggering colorectal cancer. Scott E. Devine, senior author, associate professor of medicine at the University of Maryland School of Medicine in Baltimore and colleagues, focused on a transposon called L1. It was thought about 25 years ago that L1 had no effect. Studies have shown it is active in the brain and body and in diseases, including some types of hemophilia and many cancers since then.

Prof. Devine and colleagues reported in 2010 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 are very active in lung cancer genomes. No study had found a link between L1 and cancer, despite these discoveries. The team decided to investigate the idea that perhaps L1 triggers cancer by causing mutations in genes that suppress tumors. They then concentrated on how L1 affects a tumor suppressor gene called APC, which is known to be mutated in around 85% of colorectal cancer cases.

Tumors from 10 patients were screened and the researchers found evidence of L1 insertions into the APC gene in the case of one patient. They were not found in healthy tissue. The researchers reported that one new L1 insertion inactivates the APC gene. Prof. Devine says such gene silencing allows tumors to grow unhindered. They 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 triggered colorectal cancer by mutating the APC gene. The new L1 insertion also pairs up with a mutation in the patient’s second copy of the APC gene and acts via a two-hit pathway to trigger cancer.

The patient whose tumor led to the discovery also had a strong family history of cancer, leading them to suggest that certain groups or families are more prone to cancers with active L1 insertions.

This particular study therefore shows how transposons can promote disease, but it is important to note they likely also help normal cell function since they make up a large portion of our DNA. Actually, 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.

–Dr Fredda Branyon