Understanding how diffuse gliomas evolve

• Cancer

Contribution to Nature publication

The GLASS Consortium, involving Prof Simone P. Niclou from LIH, aims to characterise diffuse glioma cells both before and after therapy to find out how they change and why this form of malignant brain cancer is so difficult to treat. Initial findings published in Nature in November 2019 provide a foundation for further research and the opportunity for the clinical community to predict the effectiveness of newly developed treatments.

Treatment limitations

Until relatively recently, cancer was viewed as a single disease with sub-types based on where in the body it arose. The advent of detailed molecular analysis has shown that the situation is far more complex and that there can be many sub-clonal cell populations even within a single tumour. Therein lies a significant problem for effective therapy: eradicating one type of cancer cell may leave another unaffected, and it may actually confer a competitive advantage to it.

The most common malignant brain tumour in adults, Glioblastoma, is also one of the most difficult cancers to treat. It invariably relapses despite surgical, radiotherapeutic and/or chemotherapeutic interventions. While the initial molecular characteristics have been well described in gliomas, their subsequent evolution under treatment stress remains unknown.

Highly variable tumour evolution

To address the problem, the GLASS Consortium has begun investigating the dynamics of molecular changes in gliomas over time. Their findings indicate highly variable and patient-specific trajectories of genomic alterations in gliomas. The researchers obtained data for multiple time points from 285 patients treated at 35 hospitals. In the end, they selected high quality tumour samples representing the three major subtypes of diffuse glioma from 222 patients at two time points each, which they named “initial” and “recurrence”. The analyses demonstrated the highly variable nature of gliomas, but provide a framework for effective study of glioma evolution and treatment response.

Among the interesting findings were that when glioma cells are challenged by anti-cancer treatment such as radiation and chemotherapy, they do not evolve in a consistent manner. There are common features between patient samples, such as hypermutation, a very high rate of mutation in the genome, and aneuploidy, in which entire chromosomes are lost or acquired through cell division dysfunction. Yet, following early events that drive cancer initiation and progression, their evolution often appears to be random instead of proceeding down predictable paths.

“More data are needed to fully understand glioma evolution, but the GLASS resource provides an excellent foundation to more effectively study both evolution and treatment response”

says Prof Roel Verhaak from The Jackson Laboratory (Bar Harbour, United States) who led the study.

“Collectively, these findings will help us determine what treatment approaches will result in the greatest removal or killing of glioma cells possible”.   

The joint effort of the GLASS Consortium brings important insight into how to improve the clinical prognosis for glioma patients worldwide. It also provides the largest database of sequential glioma tumour profiles to date.

This news item is derived from a press release of the Jackson Laboratory.