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Job Title
Research Assistant
Academic Rank
Staff/Research Assistant
Department
Neurosurgery
Authors
Hia S. Ghosh, BS, Ruchit V. Patel, BS, Eleanor Woodward, BS, Noah Greenwald, BS, Varun M. Bhave, BS, Eduardo Maury, PhD, Samantha E. Hoffman, BS, Yvonne Li, PhD, Hersh Gupta, BS, Liam F. Spurr, BS, Mehdi Touat, MD, Frank Dubois, MD, Andrew D. Cherniack, PhD,, Gino Cioffi, MPH, E. Antonio Chiocca, MD, PhD; David A. Reardon, MD, Patrick Y. Wen, MD, David Meredith, MD, PhD, Sandro Santagata, MD, PhD, Jill S. Barnholtz-Sloan, PhD, Keith L. Ligon, MD, PhD, Rameen Beroukhim, MD, PhD, Wenya Linda Bi, MD, PhD
Principal Investigator
Wenya Linda Bi, MD, PhD
Categories
Tags
The Cancer Genome Atlas project (TCGA) revolutionized the classification of gliomas through molecular characterization (Nature, 2008). Since 2008, molecular and prognostic statistics from TCGA have been a reference-point and have guided the development of treatment strategies. However, TCGA only investigated gliomas that met strictly-defined histologic criteria, perhaps incompletely representing the tumor heterogeneity seen in clinical practice. To address this, we aggregated 4,400 molecularly annotated gliomas- one of the largest multi-institutional cohorts to-date (non-TCGA). We investigated modern outcomes, genomic diversity, and prognostic features among adult-type gliomas (glioblastoma, IDH1/2-mutant astrocytoma (IDHmut-astrocytoma), and oligodendroglioma).
The non-TCGA cohort may better represent outcomes in the patient population. Overall survival (OS) was significantly higher in the non-TCGA cohort’s glioblastomas (Non-TCGA=19.0mo,TCGA=15.0mo), IDHmut-astrocytomas (Non-TCGA=11.4yrs,TCGA=7.3yrs), and oligodendrogliomas (Non-TCGA=25.6yrs,TCGA=11.3yrs). Furthermore, white race was associated with improved OS in non-TCGA but not in TCGA.
Through the non-TCGA cohort’s statistical power, we elucidated canonical and novel prognostic molecular alterations across glioma subtypes. We defined a rare subpopulation of aggressive IDHmut-astrocytoma with EGFR-amplification (an alteration common in glioblastoma). We also identified the additive, harmful effect of CDKN2A/B loss on survival (no-loss=best survival, 1-copy-loss=intermediate, and 2-copy-loss=worst). Furthermore, our findings highlight how certain molecular alterations may drive the well-established link between age and patient outcome.
The Cancer Genome Atlas project (TCGA) revolutionized the classification of gliomas through molecular characterization (Nature, 2008). Since 2008, molecular and prognostic statistics from TCGA have been a reference-point and have guided the development of treatment strategies. However, TCGA only investigated gliomas that met strictly-defined histologic criteria, perhaps incompletely representing the tumor heterogeneity seen in clinical practice. To address this, we aggregated 4,400 molecularly annotated gliomas- one of the largest multi-institutional cohorts to-date (non-TCGA). We investigated modern outcomes, genomic diversity, and prognostic features among adult-type gliomas (glioblastoma, IDH1/2-mutant astrocytoma (IDHmut-astrocytoma), and oligodendroglioma).
The non-TCGA cohort may better represent outcomes in the patient population. Overall survival (OS) was significantly higher in the non-TCGA cohort’s glioblastomas (Non-TCGA=19.0mo,TCGA=15.0mo), IDHmut-astrocytomas (Non-TCGA=11.4yrs,TCGA=7.3yrs), and oligodendrogliomas (Non-TCGA=25.6yrs,TCGA=11.3yrs). Furthermore, white race was associated with improved OS in non-TCGA but not in TCGA.
Through the non-TCGA cohort’s statistical power, we elucidated canonical and novel prognostic molecular alterations across glioma subtypes. We defined a rare subpopulation of aggressive IDHmut-astrocytoma with EGFR-amplification (an alteration common in glioblastoma). We also identified the additive, harmful effect of CDKN2A/B loss on survival (no-loss=best survival, 1-copy-loss=intermediate, and 2-copy-loss=worst). Furthermore, our findings highlight how certain molecular alterations may drive the well-established link between age and patient outcome.
