Taking these abovementioned data into consideration, we suggest a mechanism involved in melanoma by which NSD1′s loss-of-function is associated with a reduced epigenetic activating mark H3K36me1/2, therefore creating an epigenetic imbalance in favor with the accumulation of H3K27me3 on promoter regions of APC, leading to Wnt/β-catenin pathway regulation and subsequently to melanoma progression and immune resistance (Figure 4). The gene discussed is NSD1; the disease is melanoma.