Indeed, in most PKA-dependent tumours that were analysed, PKA activation resulted from germline mutations of PRKAR1A or GNAS. Although β-catenin was found activated in these tumours on the basis of immunohistochemical analyses, CTNNB1 somatic mutations were mostly found in larger tumours or macronodules that developed in the context of micronodular lesions36, 38. Here, GNAS is linked to neoplasm.