New technique detects genetic mutations in brain tumors during surgery within just 25 minutes

(Press-News.org) A research team in Japan has developed an innovative system that can accurately detect genetic mutations in the brain tumor within just 25 minutes. Genetic mutations are crucial markers for diagnosis of brain tumors.

Unlike conventional genetic analysis methods, which typically take one to two days to obtain results, this new system allows surgeons to identify genotyping of brain tumors and determine optimal resection margins during surgery.

The new system succeeded in detecting mutations in isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoters. These mutations are key markers for diagnosis of diffuse glioma—the most common type of brain tumor—which exhibit highly infiltrative nature. The findings were published in the journal Neuro-Oncology.

The research team at Nagoya University Graduate School of Medicine, led by researchers Sachi Maeda, Fumiharu Ohka, and Professor Ryuta Saito, developed this system to improve diagnostic accuracy during surgery.

The system utilizes the GeneSoC® high-speed real-time PCR device, which incorporates microfluidic technology, in combination with the team's original protocol that enables high-quality DNA extraction using only heat incubation.

The researchers evaluated the sensitivity and specificity of the system in 120 cases of brain tumors. They collected tumor tissue samples from patients and quickly extracted the DNA. They also assessed the presence of IDH1 and TERT promoter mutations, intraoperatively.

To verify the accuracy of the new system, the researchers compared its results with those obtained from a conventional DNA sequencing method called Sanger sequencing. While Sanger sequencing is widely used in clinical examinations and research, it usually takes one to two days to provide results, which makes it impractical for intraoperative genotyping.

The comparative verifications demonstrated that the new system exhibits high diagnostic accuracy, with 98.5% sensitivity and 98.2% specificity for detection of IDH1 mutations, as well as 100% sensitivity and specificity for detection of TERT promoter mutations.

The average analysis time per sample was 21.86 minutes for IDH1 mutations and 24.72 minutes for TERT promoter mutations. These findings demonstrated the effectiveness of this new system in aiding real-time surgical decisions.

Next, the researchers aimed to define the boundaries between normal brain tissue and tumors during surgery by taking samples from multiple areas within the same patient and checking for the presence of genetic mutations at each site. This approach was based on the concept that identifying molecular abnormalities during surgery could help surgeons determine the margins for tumor resection more accurately.

"This concept is especially important for intraoperative decision-making for extent of tumor removal for those with IDH1 mutations, as these mutations are recognized as reliable markers for distinguishing tumor cells from surrounding normal brain cells," explained Maeda in the study. "If collected sample shows no IDH1 mutations, it likely indicates that the collected site might extend beyond the tumor boundary." Subsequent pathological findings confirmed that their new system accurately defines tumor boundaries.

Maeda concluded: "We demonstrated that our genetic analysis system enables molecular diagnosis during surgery. This system identifies tumor boundaries, helping surgeons define resection margins. This marks a significant clinical achievement. Notably, our system's ability to intraoperatively identify TERT promoter mutations—which cannot be detected through immunostaining—represents a groundbreaking advancement globally. We believe this technology will significantly enhance the precision of glioma surgery in the near future."

Funding:
This research was supported by AMED under Grant Number JP23ck0106816.
 

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