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. Author manuscript; available in PMC: 2014 Sep 28.
Published in final edited form as: Cancer Discov. 2013 May;3(5):512–519. doi: 10.1158/2159-8290.CD-12-0426

Figure 1. Distinct molecular and clinical correlates of H3F3A mutation subgroups.

Figure 1

(a) Heatmap representing differential gene expression signatures between G34 versus K27, and G34 versus wild-type, paediatric GBM specimens from Paugh 2010. Top 100 differentially expressed genes are shown for each comparison. (b) Gene set enrichment analysis (GSEA) for differential gene expression signatures identified in Schwartzentruber 2012 versus those in Paugh 2010. Top – G34 versus K27: enrichment score (ES)=0.833, p (family-wise error rate (FWER))=0.0, q (false discovery rate (FDR))=0.0; Bottom – G34 versus wild-type: ES=0.94, FWER p=0.0, FDR q=0.0. (c) Heatmap representing differential gene expression signatures between G34 versus K27, and G34 versus wild-type, paediatric GBM specimens from Schwartzentruber 2012. Top 100 differentially expressed genes are shown for each comparison. (d) GSEA for differential gene expression signatures identified in Paugh 2010 versus those in Schwartzentruber 2012. Top – G34 versus K27: ES=0.88, FWER p=0.03, FDR q=0.04.; Bottom – G34 versus wild-type: ES=0.90, FWER p=0.0, FDR q=0.0. (e) Hierarchical clustering of the integrated gene expression datasets, highlighting specific clusters of G34 and K27 mutant tumours, distinct from a more heterogeneous group of wild-type cases. G34V tumours are represented by asterisks. (f) K-means consensus clustering finds the most stable number of subgroups to be three, marked by H3F3A mutation status. (g) K27 and G34 mutant paediatric GBM in our integrated dataset have distinct age incidence profiles, with K27 tumours peaking at 7 years in contrast to G34 at age 14. The two G34V tumours were diagnosed at age 14 and 20. (h) Kaplan-Meier plot for overall survival of paediatric GBM patients stratified by H3F3A status. K27 mutant tumours have significantly shorter survival than G34 (p=0.0164, log-rank test). A single G34V case for which data was available had an overall survival of 1.4 years.