SMAD4 and pancreatic neoplasm: PanINs are preinvasive intraductal lesions (Hruban et al, 2001), and PanINs harbour many of the same genetic and epigenetic abnormalities seen in invasive ductal adenocarcinomas such as mutations of the K-ras (Moskaluk et al, 1997), p16 (Moskaluk et al, 1997; Wilentz et al, 1998), SMAD4 (Wilentz et al, 2000), p53 and BRCA2 genes (Goggins et al, 2000), and aberrant methylation of the ppENK, p16 and TSLC1genes albeit at lower frequencies than those seen in invasive pancreatic cancers (Fukushima et al, 2002; Jansen et al, 2002).