New insights into diffuse gliomas through advanced molecular profiling

Patients diagnosed with the same type and grade of diffuse glioma can experience remarkably different disease courses. Understanding the biology behind these differences is essential for improving prognosis and advancing more personalised treatment strategies.

In her PhD research, Dr Santoesha Ghisai investigated the molecular characteristics of adult-type diffuse gliomas by analysing DNA, DNA methylation and RNA profiles from a large cohort of tumour samples. A substantial proportion of these samples originated from the intercontinental CATNON randomized controlled phase III clinical trial and were molecularly profiled at the Genomics Core Facility Erasmus MC, where our expertise in genomics, transcriptomics and DNA methylation analysis alongside advanced technologies supported this large-scale study.

One of the key findings of the thesis is that DNA methylation profiling provides a more refined way to grade astrocytomas. By applying a continuous molecular grading approach, tumours could be categorised as having low, intermediate or high aggressiveness. This objective molecular grading offered improved prognostic information compared with conventional tumour grading alone, helping to explain why patients with seemingly similar diagnoses can have very different outcomes.

The research also demonstrated the importance of looking beyond the tumour cells themselves. In glioblastoma, a greater presence of supportive tissue within the tumour microenvironment was associated with poorer patient survival, highlighting the significant role of the tumour's surrounding environment in disease progression.

In addition, the thesis explored the different mechanisms by which glioblastomas activate EGFR, demonstrating that this important signalling pathway can be activated through multiple mechanisms. Using advanced molecular techniques, including single-cell approaches, the research provides a more comprehensive understanding of the biology underlying these highly aggressive brain tumours.

Studies like those used for the analysis of Dr. Ghisai demonstrate the value of combining high-quality clinical samples with advanced high throughput and genomic technologies. At the Erasmus MC Genomics Core Facility, we work closely with researchers throughout every stage of their project, from experimental design and sample processing to high-quality molecular profiling and data generation. By providing reliable genomic data and technical expertise, we help enable discoveries that advance biomedical research and support the future of precision medicine.

We warmly congratulate Dr Santoesha Ghisai on the successful defense of her PhD thesis and wish her every success in her future career.

Read the full dissertation via the link below:
Molecular characterization of adult-type diffuse glioma - Erasmus University Rotterdam