Research provides new insight into cellular composition of IDH1-mutant gliomas

Winner of the Preuss Research Award, Andrew Venteicher, MD, PhD, presented his research, Cellular Architecture of Human IDH1-mutant Gliomas Revealed Using Single-cell RNA Sequencing, during the 2016 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting.

Heterogeneity among tumor cells within human glioma underlie their ability to resist chemotherapy and radiation, ultimately leading to tumor recurrence. Mounting evidence indicates that rarer subpopulations of tumor cells are endowed with stem-like properties, which are capable of resisting chemoradiation, proliferating and causing more aggressive, recurrent tumors. Characterizing these rarer, glioma stem-like populations has been difficult due to their elusive nature.

The authors optimized a technique to isolate single tumor cells for RNA sequencing from primary human gliomas at the time of resection in consented patients. The authors performed sensitive reverse transcriptase and PCR amplification from each isolated cell and have profiled the transcriptome from over several thousand cells purified from IDH1-mutant gliomas. Using computational analysis, they searched for tumor subpopulations based on the gene expression profile within IDH1-mutant gliomas.

Comparing the gene expression profiles of tumor cells derived from IDH1-mutant gliomas demonstrates that a majority of tumor cells are differentiated along two specialized glial programs. Surprisingly, a third, rarer, subpopulation of tumor cells was also detected that express a distinct stem-like program. Consistently, cellular proliferation was restricted to this stem-like subpopulation, consistent with the existence of a stem-like compartment that is solely responsible for fueling growth of IDH1-mutant gliomas in humans. The expression signature shared among these glioma stem-like cells mirrors the signature from normal fetal neurodevelopment, suggesting that features of a neurodevelopmental program are co-opted to support the growth and maintenance of human gliomas.

Single cell transcriptome analysis in IDH1-mutant gliomas reveals three distinct subpopulations of tumor cells: two dominant populations of specialized glial-like cells and a third rarer stem/progenitor-like subpopulation capable of cellular proliferation. These results provide unprecedented insight into the cellular composition of IDH1-mutant gliomas with critical implications for disease management.

Source: American Association of Neurological Surgeons (AANS)