Diagnosing Brain Cancer
in Real Time

But that is changing, thanks to Dartmouth Health researchers. They developed a new diagnostic method that can identify tumor type in a fraction of the time—even as a patient is still in surgery.

“Our method is currently the cheapest, fastest, and most comprehensive method of its kind,” says Chun-Chieh Lin, MD, PhD, a pathologist at Dartmouth Health’s Dartmouth Hitchcock Medical Center (DHMC) and assistant professor at the Geisel School of Medicine at Dartmouth, who led development of the new method. “We’re very excited about it because instead of waiting weeks for results, this method can be done in just hours.”

The method, called “irreversible Sticking Compatible Overhangs to Reconstruct DNA,” or iSCORED for short, works by identifying a key characteristic of cancer: abnormal numbers of a gene. All of our cells carry two copies of our genes, but cancerous cells can have hundreds of copies, a phenomenon known as gene amplification.

Knowing which gene has been amplified helps identify cancer type and is an essential part of directing treatment strategy.

Researchers have traditionally looked for gene amplification using a technique called next-generation sequencing, which requires mapping the entire genome of cells from a tissue sample. This method is comprehensive but incredibly time consuming. iSCORED, on the other hand, splits up the genome and samples random genes. This reduces the testing time from multiple weeks down to just 105 minutes.

So far, Lin has tested the technique on brain tumor samples provided by a clinical team as well as from a tissue bank. In both cases, iSCORED performed remarkably well. Even though the gene sampling is randomized, iSCORED was able to identify gene amplification just as well as next-generation sequencing and other methods. The method also offers a unique capability called methylation profiling, which allows for accurate tumor classification— something that is not possible with next-generation sequencing alone. Clinical trials are now underway at DHMC as well as other partner institutions.

In addition to speed, iSCORED promises to reduce the cost of sequencing analysis from thousands of dollars to just $150 to $200 per sample. Since it uses an off-the-shelf system called a nanopore sequencer and a desktop computer for data analysis, setting up a laboratory to run iSCORED tests costs only $30,000 to $35,000—much less than the $500,000 to $1,000,000 needed for a traditional setup. This makes iSCORED more affordable for small hospitals to quickly run tests in-house instead of sending samples to a specialized lab.