Fig. 4

Proliferation expression programs in syndromic MB and associated neoplasms. A Hierarchical clustering of syndromic cases by multivariable Pearson correlation analysis. Note clustering of desmoid fibromatosis (Desm) with high-grade (HG) sarcoma, and of MB-SHH/TP53-mutant with two sporadic MB-SHH control (CTR) cases. The MB-WNT and atypical prolactinoma (Pit) show no clustering with the other tumors. B Expression programs classified in 12 color-coded functional categories for four of the syndromic tumors. Horizontal slice charts represent ≥ 5-fold overexpressed genes in each functional expression category. The respective functional category % is indicated in columns: red, predominant proliferative programs; green, predominant morphogenetic programs. The total and tumor-specific number of genes with ≥ 5-fold overexpression is indicated. Chr Rm, chromatin remodeling; TFs, transcription factors; GF, growth factor; TK, tyrosine kinase; Cell adh/org, adhesion/organization. C Overexpression ranking for the proliferation functional gene categories shown on top, and represented as box-and-whiskers plots of the overexpressed genes for the syndromic neoplasms and MB-SHH CTR. The box represents the median and quartiles, and the whiskers, the minimum and maximum values. P-values are indicated with red stars: ****p < 0.0001; ***p < 0.001; **p < 0.01. D, E Overexpression heatmap for DDR genes (D) and schematic representation of the different complexes involved in DSB-HR (DNA double-strand break repair by homologous recombination) (E). The genes labeled or boxed in blue show CN loss in the MB-SHH/TP53-mutant tumor from patient M6 (RAD50 and XRCC3 show double hit), and the gene boxed or indicated in red (RADX) shows specific massive overexpression in the M6 LFS tumors. In (E), the various protein complexes are boxed in: green for DSB sensing, red for main DSB repair components, blue for ancillary complex mediating assembly of RAD51 filaments on ssDNA, and purple for RAD51 paralogs