SMAD4 and pachyonychia congenita: Four major driver genes associated with the development and progression of PC have been identified in PC: the tumor suppressor genes KRAS (94%), TP53 (64%), SMAD4 (21%), and CDKN2A (17%) are significantly mutated [25] and mutations in BRCA1, BRCA2, ATM, and CHEK2 are the most commonly seen pathogenic germline variants.