Tumor In Situ Fluid DNA Can Reveal Recurrence Risk in Glioma

A study suggests tumor in situ fluid is a better choice when trying to extract tumor DNA in patients with glioma who underwent surgery.

A new report argues that tumor DNA derived from tumor in situ fluid (TISF) can elucidate the mutational landscape of minimal residual disease in patients who underwent glioma surgery, and help physicians understand the contours of an individual patient’s recurrence risk.

Writing in Frontiers in Oncology, authors including Xingyao Bu, PhD, of Henan Provincial People’s Hospital in China, explained that almost all gliomas will recur after surgery. However, the investigators said primary and recurrent tumors have significant heterogeneity, making treatment of the recurrence more complicated.

“At present, molecular pathology obtained after resection of glioma has been used to guide postoperative treatment,” Bu and colleagues wrote. “However, due to the heterogeneity of recurrence and primary tumor, real-time postoperative gene status of glioma may be more accurate than that of tumor tissue in guiding postoperative treatment.”

The investigators said tumor circulating DNA (ctDNA) relapse can be seen early in tumor recurrence and could theoretically be used to guide “ultra-early” treatment in glioma. However, they said there is a need to identify a method to reliably obtain meaningful levels of tumor DNA.

In the new study, the authors extracted tumor DNA from fluid present in the surgical cavity of glioma, called TISF, and performed next-generation sequencing (NGS) to determine its genetic profile. TISF samples were taken from 30 patients at 2 separate postoperative points: 1 to 2 months after the operation, and when tumor progression was identified in postoperative follow-up. Blood samples were also taken from all patients, and cerebrospinal fluid was taken from 14 patients at the time of tumor progression, the authors said.

The investigators were able to obtain tumor DNA from all of the TISF samples collected, and tumor tissue gene mutations were detected in all patients. The median number of mutations was 4, and TP53 and IDH1 were the most common mutations.

Seven patients had abnormal gene rearrangement or copy numbers, and 5 cases occurred in glioblastoma, Bu and colleagues said. Among the 7 patients, the most common was CDK4 gene rearrangement or copy number abnormalities.

“The results of TISF-DNA detection in the early postoperative period showed that only 25% of the mutant genes were the same as those in the primary tissue, while only 16% of the mutant genes were the same as those in the primary tissue at the time of tumor recurrence, indicating the heterogeneity of recurrent tumors and primary tumors,” they wrote.

The investigators said the tumor DNA detected from TISF is more sensitive than cerebrospinal fluid-derived ctDNA. While cerebrospinal fluid-derived ctDNA has been shown to be a meaningful identifier of patients at high risk of recurrence, gliomas present a special challenge, they said.

“Because of the existence of the blood-brain barrier, the detection of ctDNA in blood is very limited,” they wrote. “Although cerebrospinal fluid (CSF) may be a better source of ctDNA for glioma than blood, many related studies have shown that not all CSF can find ctDNA, the high negative rate is an undeniable fact, which brings difficulties to clinical application and dynamic follow-up research.”

TISF eludes those drawbacks, the authors said.

“The spatial fluidity of local DNA in TISF is small, and it cleverly avoids the blood-brain barrier and the circulation of cerebrospinal fluid, so there is sufficient information of tumor DNA,” they wrote.

In their conclusion, the authors said their study shows that DNA derived from TISF appears to be a meaningful tool for characterizing the genomic status of glioma, revealing the mutational landscape of minimal residual disease, and thereby managing patients based on their individual recurrence risk profile.


Yu J, Sheng Z, Wu S, et al. Tumor DNA from tumor in situ fluid reveals mutation landscape of minimal residual disease after glioma surgery and risk of early recurrence. Front Oncol. Published online October 11, 2021. doi:10.3389/fonc.2021.742037