Abstract Clear-cell renal-cell carcinoma (ccRCC) accounts for 70-80% of kidney cancers, with increasing incidence driven by improved imaging, aging populations, and rising obesity rates. No routine diagnostic tests currently predict which small renal masses will progress to large, aggressive tumors, leaving a fundamental clinical question unresolved: do lethal tumors arise with inherently aggressive molecular characteristics, or do they gradually evolve from indolent precursors? To investigate s