Abstract 769P
Background
Meningiomas account for the most common brain tumor in adult neuro-oncology patients. Homozygous deletions of CDKN2A/B have reliably shown to confer an increased risk of progression in affected patients. However, the role of heterozygous CDKN2A/B deletions remains less clear.
Methods
DNA methylation data, copy-number information and mutation data were generated on a multicenter cohort of meningiomas for a total of 970 samples. The CDKN2A/B locus was determined manually for each individual case in relation to whole chromosomal or larger segmental losses and gains in the chromosomal profile. Survival probabilities were assessed using the Kaplan–Meier method. Immunohistochemistry against p16 was performed on a subset of cases to address intratumoral heterogeneity of cases, further analyzed with artificial neuronal networks.
Results
A total of 970 meningioma cases were identified with 30 homozygous and 114 heterozygous CDKN2A/B deletion cases, 826 cases were CDKN2A/B wildtype. Meningiomas with heterozygous CDKN2A/B deletions in general did not confer an increased risk of progression compared to CDKN2A/B wildtype cases (p= 0.074). However, segmental heterozygous losses yielded a significantly worse prognosis when compared to meningiomas CDKN2A/B-wildtype (p= 0.002) and in contrast to focal heterozygous deletions (p= 0.523). Segmental heterozygous CDKN2A/B deletions were significantly more frequently associated with a higher amount of copy number variations (CNVs) than focal losses.
Conclusions
Segmental heterozygous CDKN2A/B deletions do confer an increased risk of progression compared to focal heterozygous CDKN2A/B deletions in meningioma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.