HPSE2, SDC2, SPG20, RSPO2, ZNF667, SFRP2, CHST10, HAND2, NPY, ZNF677, FIGN, GPM6A, AMPH, D4S234E, ADHFE1, CNTN1, TRPC6, GRIK3, NRXN3, GFRA1, FLT4, JAM3, UCHL1, ATP8B2, MAL, CNR1, THBD, PHOX2A, EDNRB, KIF5A, NPR3, SOX17, NTRK3, VIPR2, CD34, GRASP, CDO1, INA, JAM2, RYR2, GAS7, PDE8B, SFRP1, and PRSS1 were significantly hypermethylated and downregulated in COAD samples (Fig. 2-C, Supplement 3). The gene discussed is RSPO2; the disease is colon adenocarcinoma.