35. Integrated comprehensive genomic profiling of meningiomas: A single institutional study

Meningioma is the most common central nervous system tumor and understudied because of its benign nature. High-grade meningiomas often show poorer outcome and enriched with high-risk copy-number-aberrations (CNAs) including losses/segmental-losses of chromosomes 1p, 3p, 4p/q, 6p/q, 10p/q, 14q, 18p/q and 19p/q, CDKN2A/B homozygous-deletion (CDKN2A/B-homo) and TERT promoter-mutation (TERTp) detected by comprehensive genomic profiling (CGP) including SNP-microarray, next generation sequencing (NGS) and DNA-methylation. In this study, we performed CGP on a large series of meningioma.

We identified 122 (45.2%) cases with high-risk CNAs in 270 cases assessed, including 33 WHO-grade-I, 67 WHO-grade-II and 22 WHO-grade-III. Fifty-one (41.8%) cases had hypodiploidy characterized by losses of 22, 14, 10, X/Y, 6 and 8; Eighteen (14.8%) showed polyploidy with relative losses of 1p, 14, 18, 6 and 10. In 53 (43.4%) cases with near-diploidy, half showed complex CNAs with losses/segmental-losses involving 1p, 3p, 19p,14q and 6q. Five cases (4.1%) showed CDKN2A/B-homo. NGS performed in 30 cases revealed mutations in NF2 (n=20), ARID1A (n=7), MSH6 (n=4). Seven (6.6%, 7/106) had TERTp mutation. Methylation profiling matched classifier for meningioma in 92% (79/86) of cases tested. CGP upgraded 58% WHO-grade-I and 67.2% WHO-grade-II tumors to WHO-grade-II and III, respectively. Although follow-up data is limited, 51 patients (41.8%) had tumor recurrence.

Our study showed that meningiomas are enriched by high-risk CNAs even in low-grade tumors, less frequent TERTp mutation or CDKN2A/B-homo. CGP is of clinical importance for tumor molecular characterizations. CGP should be utilized clinically and integrated in future WHO classifications for tumor grading and risk stratification.