Figure 2
Deregulated expression of cell adhesion molecules in BMI1-high; TP53-low Group 4 MB. (A) Box plot representation of BMI1 expression across a cohort of 282 primary MB profiled on Affymetrix 1.1ST gene arrays. BMI1 was significantly overexpressed in Group 4 MBs versus other molecular subgroups (p = 9.18e-12). Conversely, TP53 was significantly downregulated in Group 4 versus other molecular subgroups (p = 1.18e-25). (B) Z-score analysis of 282 non-WNT primary MBs revealed 32%, (61/188) of Group 4 MBs demonstrated relatively high levels of BMI1 with concomitant reduced levels of TP53, whereas 18% of MBs demonstrated relatively low levels of both BMI1 and TP53. Between these two populations there was a statistically significant difference in BMI1 expression, of 1.76-fold. (C) Unsupervised hierarchical clustering (HCL) of the top 1500 most differentially expressed genes demonstrated that these two Group 4 molecular variants (BMI1-high, TP53-low versus BMI1-low, TP53-low) largely cluster apart. (D) Molecular Signature Database (MSigDB) analysis of differentially expressed genes between BMI1-high, TP53-low versus BMI1-low, TP53-low Group 4 MBs identified significantly (FDR q < 0.05) over-represented Gene Ontologies (GO) intrinsic to the plasma membrane and critical for cell migration (E) Box plot representation of the expression of thrombospondin and laminin family members in BMI1-high, TP53-low versus BMI1-low, TP53-low Group 4 MBs identified in Bmi1-/- GCPs and human MB cell line upon BMI1 knockdown.