PIK3CA and hamartoma: Alternatively, hamartomas could result from permissive alleles introduced by mutations in related genes, such as concomitant SDHB-D mutations or KLLN promoter hypermethylation, which are thought to confer a greater risk of malignant transformation (Bennett et al., 2010; Mahdi et al., 2014; Ni et al., 2012), or in another component of the PI3K-AKT signalling pathway.