New research shows a more significant role of genetic predisposition in adults with glioblastoma

A recent study published in npj Genomic Medicine shows that hereditary predisposition in adult glioblastoma patients is more common than previously assumed. Using whole-genome sequencing (WGS), researchers were able to precisely identify which germline variants contribute to the development of this aggressive brain tumour. These findings offer insights that may influence both scientific understanding and daily clinical care.

With the publication of Whole genome sequencing-based analysis of genetic predisposition to adult glioblastoma, an important next step has been taken in understanding hereditary risk in adult patients.
First author and clinical researcher Mark van Opijnen and clinical molecular geneticist Roelof Koster were closely involved in the study. They explain the key findings, the relevance for patients, and the value of the Hartwig Medical Foundation dataset.

Hereditary predisposition in one in ten adult patients

The analyses show that approximately one in ten adult patients with glioblastoma has a hereditary predisposition.
“Among slightly more than 10% of patients, we identified a germline variant strongly associated with hereditary glioblastoma,” says Mark van Opijnen. “In 60% of those cases, this link was further supported by additional abnormalities revealed through WGS. This confirms that genetic predisposition plays a role in adult glioblastoma more often than previously recognised.”

Roelof Koster explains which variants were most frequently observed.
“In these patients, we detected changes in well-known DNA repair genes such as MSH6, PMS2 and BRCA1. Previously, hereditary predisposition was mainly linked to young patients or families with multiple brain tumours. Our study shows that even in unselected adult patients, hereditary factors can contribute. Using WGS, we could demonstrate that these variants indeed played a role in tumour development.”

Relevant for patients and their families

The findings have clear implications for clinical practice and genetic counselling.
“This study shows that glioblastoma is not always purely coincidental,” Koster says. “DNA analysis helps us better understand why a tumour develops. This can be relevant for the patient, for example when considering treatment options, but also for relatives who may benefit from testing or follow-up.”

Van Opijnen stresses the importance for patient communication.
“These results help us better inform patients about what WGS may reveal. They may also support the development of treatments tailored to this specific patient group.”

The Hartwig Medical Foundation database

According to the researchers, the study would not have been possible without data from the Hartwig Medical Foundation.
“The Hartwig database was used to obtain all genomic information for these patients. Without it, this study would not have been possible,” says Van Opijnen.

Koster highlights why the dataset is so valuable.
“Because tumour and blood DNA are available together, somatic and germline changes can be analysed in one workflow. The WGS pipeline developed by Hartwig is reliable and clinically validated, making the results suitable for both research and patient care.”

Joep de Ligt from Hartwig also supported the study, where RNA was used in part of te the analyses .
“For some DNA variants, it is difficult to predict their functional impact, such as splice variants. In this study, RNA data were generated for most patients (80%), which greatly helped with interpretation.”

Further research and increased attention for genetic diagnostics

The findings provide a foundation for future research into hereditary glioblastoma.
Van Opijnen notes that a logical next step would be to confirm these findings in a larger patient group. ‘Additional studies focusing on families could also help clarify inheritance patterns.’

Koster emphasises the relevance for clinical diagnostics:
“My contribution mainly involved molecular and hereditary diagnostics. Further clinical translation, such as treatment or follow-up studies in glioma, lies with colleagues who work in neuro-oncology on a daily basis.’
He hopes the results will increase awareness of the importance of genetic diagnostics in brain tumours and strengthen the role of WGS and hereditary testing in routine care.

New insights through WGS

This study demonstrates the value of comprehensive DNA analysis in understanding glioblastoma in adult patients. The confirmation that hereditary predisposition is more common than previously thought, provides new perspectives for patient care, family counselling and future research into targeted treatments.

About Roelof Koster:

Roelof Koster is a Laboratory Specialist in Clinical Genetics (LSKG) at the Netherlands Cancer Institute – Antoni van Leeuwenhoek. He specializes in molecular and hereditary diagnostics. Together with his colleagues, he translates complex NGS data into clinically relevant insights, thereby contributing to accurate diagnoses, optimal treatments, and the identification of patients with a hereditary predisposition.

About Mark van Opijnen:

Mark van Opijnen has worked as a physician-researcher with patients with recurrent glioblastoma and will defend his PhD on this topic on January 7, 2026.

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