Fig. 2. Alterations in chromosome structure underlie intratumor heterogeneity in high grade meningioma.

Clonal evolution in WHO grade II and grade III meningiomas M6 a–c, M7 d–f, M12 g–i, and M13 j–l. a, d, g, j 3D stereotactic meningioma sampling maps reconstructed from preoperative MR imaging. Patient orientation is represented by the model on the bottom right of each panel. Scale bar, 5 cm. b, e, h, k Intratumor phylogeny based on clonal ordering of copy number variants derived from methylation analysis suggests that chromosomal structural alterations are an early event during meningioma growth. Clonal variants are shown in black, shared variants are shown in blue, and private variants alterations are shown in gray. c, f, i, l RNA sequencing principal component (PC) analysis reveals that approximately 50–78% of gene expression variation among spatially-distinct meningioma samples from individual tumors is explained by the first two principal components. Differences in immune, GPCR and hormone signaling, and mesenchymal genes delineate samples within individual meningiomas. Samples from spatially distinct meningioma samples are color-coordinated by tumor-of-origin.