Interestingly, tumor suppressors classically associated with PDAC, such as p53 (Trp53), Cdkn2a/Ink4a, Pten, Brca2, and Smad4, were not significantly downregulated in the absence of Ptf1a (data not shown), leading to the notion that the susceptibility of Ptf1a cKO pancreata to KRAS involves a novel mechanism distinct from canonical tumor suppression pathways. This evidence concerns the gene SMAD4 and neoplasm.