Reconstruction of kidney renal clear cell carcinoma evolution across pathological stages.

Although numerous studies on kidney renal clear cell carcinoma (KIRC) were carried out, the dynamic process of tumor formation was not clear yet. Inadequate attention was paid on the evolutionary paths among somatic mutations and their clinical implications. As the tumor initiation and evolution of KIRC were primarily associated with SNVs, we reconstructed an evolutionary process of KIRC using cross-sectional SNVs in different pathological stages. KIRC driver genes appeared early in the evolutionary tree, and the genes with moderate mutation frequency showed a pattern of stage-by-stage expansion. Although the individual gene mutations were not necessarily associated with survival outcome, the evolutionary paths such as VHL-PBRM1 and FMN2-PCLO could indicate stage-specific prognosis. Our results suggested that, besides mutation frequency, the evolutionary relationship among the mutated genes could facilitate to identify novel drivers and biomarkers for clinical utility.