Abstract Glioblastoma multiforme is the most fatal form of brain tumor, distinguished as an aggressive growth and assists annexing by cell relocation and mortification of extracellular matrix with average survival rate of approximately 6-14 months. The majority of patients suffer recurrence due to molecular heterogeneity of glioblastoma and deregulation of many signaling pathways involved in proliferation, survival, and apoptosis. However, genetic profiling of the tumor is shown to classify disease and therapy response. Although brain surgery is involved for tissue collection, repeated tumor biopsies may be necessary for accurate genotyping over the course of the disease. While the detection of circulating tumor DNA (ctDNA) in the blood of patients with primary brain tumors remains challenging, sequencing of ctDNA from the tissue may provide an alternative way to glioblastoma genotype with morbidity and lower cost. We therefore evaluated the depiction of the glioblastoma genome in tissue from 40 patients with glioblastoma. Here we demonstrated that tumor-derived DNA was detected in tissue from 40 patients and was associated with disease load and adverse effect. The genomic landscape of glioblastoma in the tissue included a broad spectrum of genetic alterations and directly resembled the genomes of tumor biopsies. Alterations that were found during tumorigenesis and mutations in the metabolic pathway gene isocitrate dehydrogenase (IDH1, IDH2) were shared in all matched ctDNA-positive tissue-tumor pairs, whereas growth factor receptor signaling pathways showed significant progress. The ability to monitor the evolution of the glioblastoma genome through an invasive technique could advance the clinical application and use of genotype-directed therapies for glioblastoma, one of the most aggressive human cancers. Citation Format: Rashmi Rana, Rajesh Acharya, Satnam Singh Chhabra, Sunila Jain. Clinical significance of liquid biopsy in glioblastoma patients through tissue analysis abstract. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A32.