Hh-pathway genes and their deleterious mutations observed in 841 patients with CLL. (A) Reactome FI Network of Hh signaling pathway identified. Mutated genes (circle shape); genes involved in >1 pathway (red); genes connected but not mutated (diamond shape); and genes found mutated in this study (square shape). Extracted FIs involved in activation, expression regulation, or catalysis are shown with an arrowhead on the end of the line; FIs involved in inhibition are shown with a 'T' bar. (B) Localization and type of 100 deleterious mutations in genes affecting Hh signaling pathway: missense mutations are represented by orange circles, and frameshift and nonsense mutations are represented by blue and red circles, respectively. Two splicing mutations in MED12 and FBXW7 are not included in this figure. Each circle represents a unique mutation; for mutations recurring in >1 individual, the number of individuals is indicated in parentheses. The number of mutations for each gene is indicated below each gene name. (C) Schematic representation of Hh-pathway genes found to be mutated in this cohort as well as in other hematologic diseases. Activation is indicated by green arrows and inhibition by red crossbars. Dashed red crossbar indicates that MED12 inhibition by GLI3 has been reported by Zhou et al⁶⁶  while MED12 inhibition by GLI2 is postulated by similarity. The image was modified from Qiagen’s original copyrighted image by Emanuela M. Ghia. The original image may be found at https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=220. Please see the Qiagen website for the full terms of use. (D) Allelic fractions of each deleterious mutation observed in Hh-pathway genes are indicated by blue dots. The allelic fraction mean ± standard deviation about the mean, for each gene, are indicated in black. The chromosome location of each gene is indicated above the graph.