A study led by researchers from Duke Cancer Institute identifies genetic markers to classify previously undetermined glioblastomas
Glioblastoma is an aggressive type of brain tumour that affects approximately 74,000 individuals across the globe, annually.
The majority of glioblastomas can be classified into two molecular subgroups based on mutations in either the regulatory region of the telomerase reverse transcriptase (TERT) gene or in the proteins isocitrate dehydrogenase 1 or 2 (IDH).
However, approximately 20% of glioblastomas lack either of the aforementioned mutations and have no established markers with which they can be classified.
The study, recently published in Nature Communications, researched the genetic landscape of these unclassified tumours. The study's findings report new mutations, which include alterations to the DNA close to the TERT gene, as well as changes to the SMARCAL1 and ATRX genes.
These mutations encourage tumour growth by promoting telomere maintenance. Telomeres are pieces of DNA that protect the ends of chromosomes. Under normal circumstances, telomeres shorten with age and eventually trigger a signal that leads to a cell's natural death.
However, certain mutations prevent telomere shortening, allowing cells to become immortal and promote tumour growth.
These new mutations are present in other tumour types as well, potentially providing a new target for drug therapies.
"Tumour cell telomere maintenance is a very promising area for drug research," said Professor Yan, co-author of the study. "But it's extremely important to understand what's driving the cell's immortality. Cancer cells can possibly switch from one mechanism to another when they are targeted, so understanding the different genetic pathways can help develop therapies that address this resistance."
These findings improve our understanding of glioblastomas and provide a foundation for future research to then target these alterations with therapies.