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Figure 2. Molecular characteristics of ASCP and PACC. Left- Adenosquamous carcinoma of the pancreas (ASCP) is characterized by KRAS, MYC and TP63ΔN activation. Epigenetic changes cause loss of expression of chromatin-modifying genes such as KDM6A and KMT2C/D as well as molecular determinants of endoderm fate leading to expression of squamous programs. Many of the usual mutations present in PDAC also occur in ASCP. Like PDAC, ASCP is known to have a dense and prolific desmoplastic stroma that is enriched in immunosuppressive immune cells. Right- Pancreatic acinar cell carcinoma (PACC) is not defined by changes in single genes. Mutational signatures suggest that impairment of the DNA damage repair system is frequent in this tumor type. Methylation and copy number changes cause downregulation of several tumor suppressors at the protein level. Activating BRAF/RAF1 mutations and fusion products have been frequently observed. The tumor is highly cellular with little stroma, extensive vasculature, and limited immune cell infiltration. Created with BioRender.com.