First report of PDCD10 somatic mutation in liver cavernous malformation

Background Liver cavernous malformation (CM) is a slow-flow venous malformation in which involved vessels appear tortuous and enlarged, often surrounded by a dense collagenous matrix. Endothelial cells (ECs) of affected vessels show disorganized junctions. Diagnosis usually occurs by computed tomography. Cavernous vessels are also observed in cerebral cavernous malformation (CCM), a disease affecting brain vasculature and occurring following mutations in KRIT1, CCM2 and PDCD10. Coexistence of brain and extra-neurological lesions has been reported. In this study, for the fi rst time, we describe the possible common molecular basis between liver and brain cavernous lesions. Methods and results Genotyping of the three CCM genes was performed on DNA purified from CM ECs. Comparison with DNA purified from control liver ECs allowed to identify several germline variants linked to CCM development. However, a novel PDCD10 rearrangement was uniquely detected in CM ECs. By TOPO-TA Cloning Sequencing, this rearrangement was characterized as an unbalanced translocation, der(7)t(3;7)(q26.1;p12.1). The translocation spans the FAT-homology domain of the PDCD10 protein, crucial for CCM2 binding and the formation of the CCM signalling complex. Conclusions Identification of the PDCD10 somatic mutation suggests a possible common pathogenesis for liver and brain cavernous lesions and allows to increase knowledge on the pathogenesis of liver vascular malformation. Further, for the fi rst time the role of PDCD10 in extra-neurological cavernous lesions was reported.