Moreover, the genomic landscape of PC has been deeply analyzed to find key mutations, such as KRAS, loss of TP53, and the inactivation of CDKN2A and SMAD4; gene overexpression and recombination, including C-Myc, BRCA 1/2, and PALB2; and mismatch repair deficiency in driving disease development, chemoresistance, intra-tumor angiogenesis, epithelial-mesenchymal transition (EMT), tumoral invasion, and metastasis [79,231,232]. Here, SMAD4 is linked to pachyonychia congenita.