Fig. 4.

Somatic events in the carriers of pathogenic variants in genes with enrichment. Somatic alterations were characterized for the carriers of germline PVs in CHEK2, MET, FH, and VHL, and age of disease onsets were compared between groups of patients with different germline variant status. (A) Comutation plot summarizing germline and somatic variants in RCC patients with germline pathogenic variants in the three significantly enriched genes as well as CHEK2. For the somatic events, only variants in relevant genes are featured. The dotted horizontal line on the bar plot indicates the age of onset at 45 yr. (B) Density plot (left) and box plot (right) for the distribution of age of disease onset for the different pathogenic variant carrier groups. Adjusted p value was calculated after a one-way ANOVA with post hoc Tukey’s HDS test. ANOVA = analysis of variance; CNA = copy number alterations; HDS = honestly significant difference; NS = not significant; PV = pathogenic variant; RCC = renal cell carcinoma.