ID #308 COG Molecular Characterization Initiative in Brain Tumors: A Three-Year Single-Institution Experience
Magimairajan Issai Vanan, Meziane Brizini, Hadeel Hassan, Annie Drapeau, Colin Kazina, Patrick McDonald, Stephanie Villeneuve, Saranya Kakumanu, Marshall Pitz, Rebekah Hiebert, Tina Drimes, Marc del Bigio, Namita SinhaAbstract
Background
The Children’s Oncology Group–Molecular Characterization Initiative (COG-MCI) was locally approved at Cancer Care Manitoba in May 2022. We report our institutional experience with COG-MCI in pediatric and young adult patients with brain tumors over a three-year period (2022–2025).
Methods
Following institutional Research Ethics Board approval, relevant clinical and molecular data were retrospectively collected for patients enrolled in COG-MCI. Data included consent status, tissue availability, molecular profiling results (including methylation and germline testing), diagnostic changes, and impact on clinical management.
Results
Thirty-six patients with brain tumors were consented during the study period. Tissue was unavailable in seven patients (19.4%) due to insufficient quantity (n = 5), prior use for local testing (n = 1), or lack of surgical intervention (n = 1). One additional sample (3.4%) failed quality control due to low DNA yield or tumor cellularity <30%. Of the 28 evaluable patients, three were adults (>17 years). Turnaround times were consistently shorter with COG-MCI (mean,18.5 days; range-16-21 days) compared with local testing (> 3 weeks). Diagnostic modification occurred in six patients (21%), driven by methylation profiling (n = 5) or germline findings (n = 1). Pathogenic germline variants were identified in seven patients (24.1%), resulting in syndromic diagnoses in five cases (Gorlin syndrome, n = 2; Lynch syndrome, n = 1; Li–Fraumeni syndrome, n = 1; melanoma–astrocytoma syndrome, n = 1). Cascade testing identified pathogenic variants in four of five tested siblings. Gliomas were the most common tumor type (60.7%), followed by embryonal tumors (21%) and choroid plexus tumors (18%). Actionable molecular alterations were identified in 47% of gliomas, predominantly in low-grade tumors, leading to targeted therapy initiation in all cases. No patients were enrolled in clinical trials.
Conclusion
Our institutional experience aligns with published data demonstrating the clinical utility of comprehensive molecular profiling. Based on these findings, we recommend routine inclusion of germline testing in all patients with newly diagnosed brain tumors.