CDKN2A and neoplasm: Prospective studies further support these findings: in a cohort of 62 patients [90] pathogenic variants in TP53, CDKN2A, HRAS and PIK3CA detected in tumor or circulating DNA were associated with worse overall survival, while another study focusing on TP53-mutated ctDNA [91] confirmed its link with advanced nodal involvement and shorter progression-free survival, underscoring TP53 as a pivotal determinant of poor prognosis.