An international research team has found that when diffuse glioma recurs, there are apparent changes in tumor cells, and tumors with a specific phenotype have a poor prognosis.
Diffuse glioma is a tumor that occurs in the brain's astrocytes, an intractable disease with frequent recurrence and exacerbation even after surgery or radiation therapy. However, there is little information about what causes the treatment resistance.
The team -- led by Professor Paek Sun-ha and Doctor Moon Hyo-eun at Seoul National University Hosptial and Doctors Frederick Varn and Roel Verhaak at Jackson Laboratory -- expanded the longitudinal analysis data collected by the GLASS consortium in 2018 to check the changes in the genetic and cellular composition before and after glioma recurrence and analyzed the recurrent tumor cell data of 304 glioma patients from various angles.
They confirmed that tumor cells change genetically and cytologically during glioma recurrence, and there are changes in intracellular microenvironment interactions.
The researchers emphasized that this change is significant for discovering specific phenotypes that can be used as prognostic factors of glioma.
Changes in recurrent tumors have three phenotype groups -- neuronal, mesenchymal, and proliferative. Each phenotype formed according to the mutation status of the isocitrate dehydrogenase (IDH) gene, and the team found that they had different characteristics and survival rates.
Although neuronal and mesenchymal phenotypes are gliomas without IDH mutations, neuronal has no relationship with the patient's survival rate, while mesenchymal phenotype has a low survival rate.
The proliferative phenotype occurs in gliomas without IDH mutations and in IDH mutated gliomas that have deficient in the CDKN2A gene or are hypermutated. This phenotype has a low patient survival rate and active tumor growth due to the proliferation of new cells.
The researchers emphasized that these results provide new guidelines for understanding the progression of diffuse glioma, help determine the disease trajectory of patients, and guide clinical decision-making for recurrent tumors.
"Treatment resistance of diffuse gliomas is an important challenge to overcome to improve patients' quality of life," Professor Paek said. "Based on the fact that tumor cells change by genetic and microenvironmental factors, we expect to build a therapeutic response predictive model for glioma."
CELL published the results of the study.