In that respect, complexities in evaluating the role of RAS mutations in driving different tumor phenotypes are highlighted by recent evidence showing that distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumor suppressor alterations (Cdkn2a, Trp53, Tgfβ-pathway), direct variations of oncogenic RAS dosage gain, to drive the early progression of PDAC and shape its downstream biology [51]. This evidence concerns the gene TGFB1 and neoplasm.