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.

Fig. 1

Usual course of glioma management. GLASS would improve the assessment of gliomas, particularly the prediction of malignant transformation, treatment monitoring, and assessment of tumor alterations noninvasively with imaging and/or liquid biopsies. SMDT (tumor board): specialist multidisciplinary team; RT: radiotherapy.

Fig. 2

Simplified glioma evolution models. The glioma-initiating cell evolves into the tumor at diagnosis with selective pressures resulting in intratumoral heterogeneity. Recurrent tumors share few or the majority of the somatic alterations seen in the diagnostic tumors depending on the evolutionary pattern (linear, branching, or ancestral evolutions). Subclones may be marked by mutations or extrachromosomal DNA elements.