In cancer research, scientists usually look for cancer genes by scouring the genome for altered sequences — or mutations — in DNA. But a new study has now revealed that jumping genes, which customary sequencing overlooks, are also important drivers of tumor growth.
They analyzed 7,769 tumor samples from 15 different types of cancer and found 129 jumping genes that can drive tumor growth through their influence on 106 different cancer genes.
The jumping genes were functioning as “stealthy on-switches” in 3,864 of the tumors that the team analyzed. These tumors came from breast, colon, lung, skin, prostate, brain, and other types of cancer.
A recent Nature Genetics paper gives a full account of the study.
By identifying jumping genes as potential genetic targets, the findings break new ground in the quest for novel cancer treatments.
“If you,” says Ting Wang, who is a professor of medicine in the Department of Genetics, “perform typical genome sequencing, looking for genetic mutations driving cancer, you’re not going to find jumping genes.”
Cancer develops when the genetic instructions that govern how cells function, particularly how they mature and divide, undergo certain changes.
Some of the genetic changes that cause cancer alter the body’s natural curbs on cell growth; others might disrupt the structure and function of proteins that carry out the work of cells and keep them in good repair.
Genetic changes with the potential to cause cancer can pass on from parent to child. They can also arise during a person’s lifetime, such as during cell division, or in response to ultraviolet radiation, carcinogens in tobacco smoke, or other environmental factors.
There are different types of genetic changes. Some affect just a single building block of DNA, while others can duplicate, omit, or rearrange long sequences of building blocks.
Another way that genetic changes can lead to cancer does not alter the DNA itself but changes its ability to express its instructions. This type of change is called epigenetic. One way that it happens is through chemical tags that attach to the DNA.
It is normal for cells, even healthy ones, to have genetic alterations, but cancer cells tend to have many more of these. Each person’s cancer will have its own pattern of genetic changes, and even in the same tumor, different cells could have different genetic fingerprints.
Jumping genes, which scientists call transposable elements, are sequences of DNA that can move around in a genome. They “come in many different forms and shapes,” and scientists need specialized tools to analyze them.
Thanks to improved and powerful techniques, scientists are realizing that jumping genes are very active in the genome and that perhaps “they should no longer be marginalized.”
How jumping genes made their way into the human genome during evolution is a hot question. Some people have argued that viral infection has been a common route.
Previous studies have shown that specific elements within jumping genes can influence the expression of cancer genes. However, these have not investigated such events in much detail or explored how common they might be in different cancers.
So, Prof. Wang and his team decided to address these points by using tumor samples from The Cancer Genome Atlas program.
They discovered that jumping genes are a feature of many cancers with accelerated tumor growth.
It appears that in these more aggressive cancers, the jumping genes behave as “cryptic switches” that switch on cancer-related genes that are usually silent — and keep them switched on.
A critical finding of the study is that while jumping genes appear to be widespread in cancer, their pattern of presence and influence varies across cancer types.
“Jumping genes are more important in some cancer types versus others, but on average, we found at least one of them activating a cancer gene in about half of all the tumors we studied,” Prof. Wang explains.
He suggests that giving doctors this type of information could help them decide whether to treat particular cancers “more aggressively.”
“It also provides new targets to study for future cancer therapies,” he adds.
Another important finding was that jumping genes operating as stealthy on-switches were more prevalent in cancers whose DNA shape was more open. The genome typically keeps DNA tightly closed. Open-shaped DNA is more likely to lose some of its function.
“A lot of what transposable elements are doing in our genome is still a mystery. This study is the first detailed outline of their important roles in cancer.”
Prof. Ting Wang