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Multi-step carcinogenesis hypothesis of pancreatic cancer. As genetic alterations of Kras, p16INK4a, p53, Smad4 and BRCA2 accumulate, the pre-cancer lesion pancreatic intraepithelial neoplasia (PanIN) occurs and progresses from low-grade (1A, 1B) to high-grade (2, 3) and to invasive cancer. The frequency of each genetic alteration at the invasive cancer stage is also shown.
