RSPO2 abnormal transcripts result from read-through in liver tumours with high ß-catenin activation and CTNNB1 mutations

Thomas Longerich and collaborators1 recently published an intriguing observation in hepatocellular adenoma (HCA) showing an activation of the Wnt/s-catenin signalling pathway without CTNNB1 or APC mutations. The authors identified a recurrent deletion leading to a fusion between a short interspersed nuclear element (SINE) sequence and RSPO2 gene in three HCAs and three hepatocellular carcinomas (HCCs) all activated for s-catenin, including one tumour with CTNNB1 mutations and five tumours without APC or CTNNB1 mutations. The authors proposed RSPO2 fusion as a recurrent mechanism of s-catenin activation in liver tumourigenesis. Following this original observation, we analysed the expression and rearrangement of RSPO2 in a series of 10 HCAs and 163 HCCs analysed with RNAseq. We identified a correlation of RSPO2 mRNA expression with several genes known to be positively …