Characterizing the Genomic Landscape of Brain Glioma With Circulating Tumor DNA From Tumor In Situ Fluid.

Zhiyuan Sheng,Zhaoyue Yan,Nianxuan Li,Jinliang Yu,Zhongcan Chen,Juha Hernesniemi,Ajmal Zemmar,Yong Sun,Hugo Andrade-Barazarte,Kaiyuan Deng,Sijia Li,Xingyao Bu

doi:10.3389/fonc.2021.584988

Abstract

Tumor in situ fluid (TISF) refers to the fluid at the local surgical cavity. We evaluated the feasibility of TISF-derived circulating tumor DNA (ctDNA) characterizing the genomic landscape for glioma. This retrospective study included TISF and tumor samples from 10 patients with glioma, we extracted cell-free DNA (cfDNA) from the TISF and then performed deep sequencing on that. And we compared genomic alterations between TISF and tumor tissue. Results showed that the concentration of cfDNA fragments from the patients for TISF ranged from 7.2 to 1,397 ng/ml. At least one tumor-specific mutation was identified in all 10 patients (100%). Further analysis of TISF ctDNA revealed a broad spectrum of genetic mutations, which have been reported to have clinical relevance. The analysis of concordance between TISF and tumor tissue reflected the spatiotemporal heterogeneity of glioma. Collectively, TISF ctDNA was a powerfully potential source for characterizing the genomic landscape of glioma, which provided new possibilities for precision medicine in patients with glioma.

Highlights

Glioma is a tumor with high molecular heterogeneity, its constantly evolving genetic landscape can be a huge obstacle to the clinical management of patients [1]
We retrospectively investigated whether circulating tumor DNA (ctDNA) from Tumor in situ fluid (TISF) could be a new source of liquid biopsy for precision medicine for patients with glioma
Characterizing the heterogeneity of glioma with liquid-based biomarkers is a powerful tool for precision medicine, which has been increasing the likelihood of curing malignancies [5]

Summary

INTRODUCTION

Glioma is a tumor with high molecular heterogeneity, its constantly evolving genetic landscape can be a huge obstacle to the clinical management of patients [1]. The need for precision medicine is to characterize the real-time molecular status of the tumor, which is believed to have therapeutic significance for glioma patients [4]. Characterizing Genomes of Glioma with TISF detection has proved to be of great clinical significance for a variety of solid tumors [5], such as breast [6], gastric [7], and esophageal [8] cancers. With an intraoperatively implanted reservoir, obtaining TISF postoperatively is clinically feasible and uninjurious. Based on this hypothesis, we retrospectively investigated whether ctDNA from TISF could be a new source of liquid biopsy for precision medicine for patients with glioma

MATERIALS AND METHODS

RESULT

DISCUSSION

Findings

ETHICS STATEMENT