MiRNA-9 and MiRNA-200a distinguish hemangioblastomas from metastatic clear cell renal cell carcinomas in the CNS

Abstract

Central nervous system (CNS) tumors in von Hippel-Lindau syndrome (VHL) include hemangioblastomas and metastatic clear cell renal cell carcinomas (Met CCRCC). While these tumors often show similar histologic features, differentiating them is of significant importance as Met CCRCC are higher-grade tumors with worse prognosis. No single current immunohistochemical marker unequivocally differentiates between these two entities. MicroRNAs (miRNAs) are noncoding cellular small RNA molecules that play an important role in cancer. We hypothesized that hemangioblastomas and Met CCRCC display distinct miRNA signatures enabling their histologic differentiation. MiRNAs were profiled in 10 cases each of hemangioblastomas, Met CCRCC and primary CCRCC. Ten miRNAs had greater abundance (including miR-9 (∼10-fold) and miR-135a (∼7-fold)) and 39 miRNAs were lower [including miR-200a (∼22-fold) and miR-200b (∼12-fold)] in hemangioblastomas compared with Met CCRCC. Quantitative real-time RT-PCR in 20 hemangioblastomas and 13 Met CCRCC showed a 12-fold increase in miR-9 and a 15-fold decrease of miR-200a in hemangioblastomas compared with Met CCRCC. Finally, in situ hybridization for miR-9 in 15 hemangioblastomas and 10 Met CCRCC confirmed these results. Our data suggest that miR-9 and miR-200a can distinguish between hemangioblastomas and Met CCRCC. Further, these results may also provide insight in understanding the biology of hemangioblastomas.