APC and colorectal carcinoma: LOF mutations of RNF43/ZNRF3 genes26,27 and GOF gene fusions involving RSPO2 and RSPO320,28 lead to increased cell surface abundance of WNT receptors and consequently constitutive activation of WNT signalling in the 15–20% of CRC that lack APC or CTNNB1 alterations20,21.