Extended Data Figure 10: Theoretical model of pancreatic cancer tumour progression.

Shown is the classical model of tumour evolution driven at a gradual pace (grey) and an alternate model driven at punctuated equilibrium (red). In the classical model, there is a period of latency between the driver mutations that lead to tumour development and the multiple, independent, transforming events are required for tumour development (top, grey dashed line; bottom-left schematic). In the punctuated equilibrium model, tumour development can be divided into two major events, the cancer-initiating event and cancer-transforming event (top, red dashed line; bottom-right schematic). Under this model, most mutations (indicated by ×) would accrue in an extended phase of preneoplastic tumour development. Transformation, probably due to genetic instability from copy number changes (arrow heads) ensuing from a cataclysmic event, would rapidly lead to invasive cancer and metastases. Classical drivers (KRAS, CDKN2A, TP53, SMAD4) from the PanIN progression model are overlaid onto these models. Theoretical PanIN stages are shown as P1–P3.