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Jumping into the genome

Speed read
  • “Junk DNA” can copy and insert itself into the genome
  • Genes disrupted by these transposable elements (TEs) may affect cancer development
  • Analysis of TEs open pathways to individually targeted therapies for specific cancers

When a patient is diagnosed with cancer, doctors first try to remove as much of the tumor as possible in surgery.

If cancer cells have spread further, however, doctors sometimes prescribe chemotherapy to eliminate the damaged cells.

These treatments are often grueling for patients. Patients may shed intestinal and hair cells because chemotherapy targets all fast-growing cells in the body, not just cancer cells. Some experience nausea and hair loss as a result.

Traditional cancer treatments like chemotherapy can cause adverse reactions such as hair loss and nausea. But targeting precise attributes of a tumor would attack only toxic cells and spare healthy ones. Courtesy US Air Force/Staff Sgt. Alexander Martinez.

What if there were a way for medical professionals to specifically target cancer cells at their source, eliminating only toxic cells and leaving behind critical healthy ones?

That’s the aim of Indiana University (IU) School of Medicine professor Milan Radovich and Vera Bradley Postdoctoral Fellow Robin Paul. They want to target precise attributes of an individual’s tumor by investigating one unique aspect of the human genome.

A transmissible error

Radovich says cancer can best be understood as a disease of DNA.

“When certain mutations occur in the DNA of a cell, it begins to act abnormally and becomes cancerous,” Radovich says. “We want to figure out what makes cancer tick.”

Scientists usually focus on individual genes to determine the causes of tumors. While genes do play a critical role in the growth of cancer, researchers in the past overlooked strands of DNA known as transposable elements (TEs), also sometimes known as “junk DNA.”  

With the advent of new computational technologies, we're beginning to learn more and more that this dark matter we once neglected actually plays a key role ~ Robin Paul.

“TEs will literally jump, copy and insert themselves into areas of the genome,” Paul says. “Every once in a while, transposable elements will insert themselves into the middle of a gene and when that gene is deconstructed, it will lead to the development of cancer. The question is, how do we find them?”

While scientists have known about transposable elements since Barbara McClintock’s discovery of them in the 1940s, until recently they have been considered relatively unimportant. Now, scientists recognize that TEs can cause mutations and increase or decrease the amount of DNA in the genome of the cell.

The great DNA hunt

Radovich and Paul pored over several databases to search for TEs.

They started by examining the Cancer Genome Atlas, a database of 35 cancer types in over 15,000 tumors, and the European Genome archive. They also generated data from patients as part of the IU Health Precision Genomics program.

IU School of Medicine professor Milan Radovich studies transposable elements in DNA to better understand how they affect the development of cancers. His research may lead to precision treatments tailored to individuals' needs. Courtesy Indiana University.

After downloading the genomes from these databases, the two scientists put them through next-generation sequencing technology, which fragments them into much smaller pieces for a more in-depth look at how TEs can potentially affect cancer development.

Looking at hundreds of individual examples at once can be computationally challenging. Thanks to IU’s computing cluster Mason, Radovich and Paul can process up to four terabytes of data at a time to quickly zone in on TEs within the genome.

Precisely on target

Radovich and Paul collaborate in a field known as precision medicine, which the National Institutes of Health defines as "an emerging approach” to focus as much as possible on the individual when treating disease, instead of working with a one-size-fits-all model.

“When it comes to precision medicine we're just scratching the surface on our understanding of what all the genome holds,” Paul says.

Radovich and Paul both have optimism that their knowledge of TEs will improve precision medicine in the future for treating specific cancers.

“We're learning more and more about how cancers are caused, how they're driven, how they metastasize,” Paul says. “Our hope is that eventually we'll use this information to develop better drugs, and better treatments, and better ways of combating disease.”

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