Diffuse gliomas comprise the bulk of brain cancer in adults and the most common primitive malignant brain tumours in adults.
The 2016 WHO update combines histology with tumor genetic information; glioblastoma (GBM) can be subdivided into two types, based on the mutation in codon 132 of isocitrate dehydrogenase 1 (IDH1). The majority of GBMs (90%) are IDH1-wildtype and arise de novo without previous low-grade tumor, whereas GBM IDH1-mutant progress from a precursor low-grade glioma. Latest WHO classification of these tumours introduced the concept of integrated diagnosis: a diagnosis based upon the integration of both morphological and molecular findings. For IDH-mutant lower-grade gliomas (grades II and III), a set of genetic parameters can distinguish astrocytomas from oligodendrogliomas. IDH-mutant astrocytomas (~80%
of all astrocytomas) are defined by mutations of ATRX and TP53. IDH wild-type GBM is characterized by telomerase reverse
transcriptase (TERT) promoter mutations and EGFR amplification involved in cell growth, cell cycle, proliferation, and survival.
The two groups of GBM IDH-mutant and IDH wild-type have distinct genetic and clinical profiles. Pseudoprogression, has become a major challenge in glioblastoma follow up, as only surgery or serial imaging is conclusive.Liquid biopsy is a technique that consists of the detection of circulating tumor cells and circulating tumor DNA in peripheral fluids from cancer patients. Peripheral blood has low sensitivity in CNS neoplasms, due to hampering of the blood brain barrier (BBB) to detect
CNS tumour components. It has been recently demonstrated that CSF ctDNA is more representative of brain tumour genomic
alterations than plasma.
Liquid biopsy might represent a minimally invasive and repeteable procedure which provides clinically meaningful information about both diffuse glioma and pseudoprogression
