Fig. 4
From: Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development
Molecular profiling of RTs from P0-CreC;Smarcb1 flox/flox mice. a Unsupervised hierarchical clustering of gene expression profiles from 12 P0-CreC;Smarcb1 flox/flox mouse tumors and 49 human AT/RTs43 using the 5,000 most variable transcripts. The P0-CreC;Smarcb1 flox/flox tumors distributed among the three human AT/RT molecular subgroups. Information about tumor molecular subgroups and anatomical location is displayed in the lower bars. b Unsupervised hierarchical clustering of gene expression profiles from 12 P0-CreC;Smarcb1 flox/flox mouse tumors, eight tumors from the tamoxifen inducible Rosa26-Cre ERT2 ;Smarcb1 flox/flox mouse model30 and five tumors from the hGFAP-Cre;Smarcb1 flox/flox ;Trp53 flox/flox mouse model44 using the 5,000 most differentially expressed genes. Information about tumor molecular subgroups is displayed in the lower bars. c Normalized expression level of representative genes for both of the three human AT/RT molecular subgroups: hTYR (n = 16), hSHH (n = 16), and hMYC (n = 17) and the three P0-CreC;Smarcb1 flox/flox RT molecular subgroups: mRT-Tyr (n = 5), mRT-Shh (n = 4) and mRT-Myc (n = 3). On the basis of the cluster analysis in (a), we respectively named hMYC, hSHH and hTYR the three tumor subgroups including human tumors from the MYC, SHH and TYR molecular subgroups 43. The P-value indicates the statistical significance of gene enrichment within their respective WGCNA module for each respective molecular subgroup. d–g Gene expression levels of specific SWI/SNF complex subunits (d, e) and NC developmental markers (f, g) in the three molecular subgroups of P0-CreC;Smarcb1 flox/flox RTs (d, f) and human AT/RTs (e, g). d, f RNA-Seq data are expressed in RPKM (Reads Per Kilobase of transcript per Million mapped reads). e, g graphs of microarray gene-expression intensity from dataset GSE70678. c–g RNA-Seq and microarray gene expression levels are shown using Tukey boxplots: the central lines represent the median, boxes (interquartile range or IQR) represent 50% of data ranging from the 25 to 75% quantile, whiskers represent extremes up to 1.5-fold box size, circles show outliers
