Glioma through the looking GLASS: molecular evolution of diffuse gliomas and the Glioma Longitudinal Analysis Consortium

Abstract

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal Analysis Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities and, ultimately, improved outcomes for a patient population in need.

Intratumoral Heterogeneity and Longitudinal Changes in Gene Expression Predict Differential Drug Sensitivity in Newly Diagnosed and Recurrent Glioblastoma

“…The major novelty of our study is that it integrates a multisampling approach, longitudinal transcriptomic profiling and complementary investigations using GB tissues and GSCs in the frame of the same investigation. The approach undertaken in our research meets state-of-the-art requirements outlined in the conceptual paper by the international consortium GLASS, which has emphasized the importance of considering the impact of intratumoral spatial diversity and longitudinal changes in molecular diagnostics for gliomas [14].…”

“…Furthermore, there is an emerging consensus that traditional diagnostic approaches based on analyses of a single tumor biopsy may be insufficient for implementing molecular diagnostics of GBs that are notorious for the high degree of intratumoral spatial heterogeneity [9][10][11][12][13]. Reflecting the importance of sampling strategy and treatment-driven molecular evolution in (re)shaping molecular landscapes during GB recurrence, a so-called GLASS (The Glioma Longitudinal AnalySiS, https://www.glass-consortium.org/) consortium has recently been formed to address these issues in the frame of a multicenter investigation [14].…”

Knockdown of TXNDC9 induces apoptosis and autophagy in glioma and mediates cell differentiation by p53 activation

“…Patients with low-grade glioma still cannot avoid recurrence after treatment. Still, for patients with high-level glioma, it brings specific challenges to clinical workers and patients whether to treat and what kind of treatment to take [ 20 , 21 ]. Even if surgery plus radiotherapy and chemotherapy are adopted, the prognosis is not optimistic in the later stage [ 22 ].…”

RNA processing genes characterize RNA splicing and further stratify lower-grade glioma

“…LGGs can be classified as WHO grade II or III based on histological features or as oligodendroglioma with isocitrate dehydrogenase-mutant (IDH-mutant) and 1p/19q codeletion, astrocytoma with IDH-mutant, and astrocytoma with IDH-wild-type according to the WHO 2016 integrated analysis (1,3,8). However, this classification still does not fully reflect the rate of LGG evolution and, for the OS of patients with LGGs in a stratified subgroup, is rather heterogeneous (7,8).…”