At this point, focusing on the six genes that are specifically hypermethylated in HCC (Fig. 5A-right), and noting that one of them is not expressed in either liver or HCC (CELF6), two others are not associated with changes in expression (EFNB2 and MTHFD2), and the remaining three are slightly downregulated in HCC (TSC22D1, SH3YL1 and RNF135), we questioned whether this hypermethylation status may indeed have an impact on gene expression. The gene discussed is EFNB2; the disease is hepatocellular carcinoma.