The Neurogenome study: Comprehensive molecular profiling to optimize treatment for Danish glioblastoma patients

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Background: Glioblastoma is an aggressive brain cancer with no possibility for cure. Treatment and survival have only improved slightly since 2005 when the current regime was implemented. The limited improvements in the treatment of glioblastoma may reflect our poor understanding of the disease. We hypothesize that systematically collected translational data will improve knowledge and hereby treatment. Methods: We have been performing whole exome sequencing in glioblastoma tumor tissue since 2016 and whole genome sequencing (WGS) since 2020 with the aim of offering experimental treatment. Results: We have sequenced 400+ GBM patients and from these 100+ are paired tumor samples from relapse surgery. To develop genomic profiling and to increase the information on each patient's contribution, we have initiated the Neurogenome study as of June 2022. The Neurogenome protocol is a national, comprehensive, translational, and omic protocol. It is a continuation of 2 previous protocols from 2016 and forth in our department, but with more substudies added, focusing on the translational and clinical utility. We collect and analyze data from an out-patient clinic in a systematic approach to a number of subprojects ranging from basic science to applied clinical science, including clinical trials. Conclusions: The protocol will act as a backbone for future projects in the national research center, Danish Comprehensive Cancer Center-Brain Tumor Center with the overall aim to select eligible patients for experimental treatment based upon genomic alterations. The article will present the Neurogenome setup and a presentation of selected projects that are based upon inclusion.

OriginalsprogEngelsk
Artikelnummervdad137
TidsskriftNeuro-Oncology Advances
Vol/bind5
Udgave nummer1
Antal sider8
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work has been supported by the Danish Cancer Society and by the Danish Comprehensive Cancer Center. Brain Tumor Center. Acknowledgments

Funding Information:
With a rare disease like GBM, collaboration is essential, both national and international. Genomic profiling in GBM is possible and used in the clinical setting today. We find that genomic profiling in GBM has clinical relevance and targets do exist for a subset of patients, but clinical trials are still too few. Identification of targetable alterations is crucial to increase treatment possibilities and personalized medicine programs. There is a need for more targeted treatment options through clinical trials. As pseudo-progression is a recurrent challenge in determining treatment response, new or better evaluation methods are needed, for example, by imaging or easy access to continuous biopsies. Liquid biopsies in brain cancer are in their infancy and few studies have investigated newly diagnosed GBM patients. At this time, a blood sample cannot replace a tumor biopsy, but we foresee that a project like the Neurogenome can contribute to this development, exploring a possible role of cfDNA/ctDNA as prognostic and predictive biomarkers.Funding This work has been supported by the Danish Cancer Society and by the Danish Comprehensive Cancer Center. Brain Tumor Center.

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

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