Meningiomas With Chromosomal Polysomies Reveal Nonrandom Gain of Chromosomes, Distinct Methylation Signature, and Lower Risk of Recurrence

Meningiomas are the most common primary central nervous system tumors in adults. Although the majority of meningiomas are benign, certain clinical and histopathological factors are associated with an increased risk of tumor progression and recurrence. Advances in genomic characterization of brain tumors have revealed that certain molecular characteristics such as TERT promoter mutation and chromosomal losses on 1p, 6p/q, 9p, 10p/q, 14q, and 18p/q as genomic markers are associated with aggressive behavior. However, the significance of chromosomal polysomies in meningiomas is not clear. We performed a comparative analysis of clinical, cytogenomic, and methylation profiles of a series of 25 meningioma cases with gains of multiple chromosomes and compared with 2 low-risk groups with either no copy number alterations or isolated monosomy 22. No high-risk morphologic subtypes of meningioma were linked to the polysomy group, and there were no differences in the World Health Organization Grade or progression-free survival between the study groups. Noteworthy was a nonrandom pattern of chromosomal gains, with most cases showing tetrasomy of chromosomes 5 and 20 with concurrent trisomy of chromosomes 12 and 17. Methylation profiling showed that meningiomas with polysomies had a distinct methylation signature and were predominantly Merlin-intact meningiomas. These results suggest that meningiomas with multiple polysomies are an uncommon subclass of benign meningioma that have a low rate of progression after resection and a unique genetic architecture.