(a) Bisulfite sequencing of HPP1 hypermethylated
fragment. HPP1 sequence with CpG sites is indicated (*).
(Top) Bisulfite-modified DNA of normal mucosa showing
C→T conversion. (Middle and Bottom)
Hyperplastic polyp and tumor specimens, respectively, showing
methylated (unconverted) CpG sites following bisulfite treatment.
(b) COBRA assay. A 427-bp PCR fragment cleaved by
RsaI when methylation is present in bisulfite-modified
DNA. M, 100-bp DNA ladder (Promega); N, normal mucosa; T, tumor DNA.
Histogram showing distribution of COBRA methylation in normal mucosa
(N) and tumor (T) samples and illustrating cluster of results below
30% in normal mucosa samples. (c) Differential
expression of HPP1 as indicated by the presence or absence of a 307-bp
cDNA fragment after RT-PCR in normal mucosa (N) and corresponding tumor
(T) samples. (d) Expression of HPP1 in LoVo was restored
after 12 h of treatment with the demethylating agent 5-AzaC (0.5
μM) and maintained up to 72 h posttreatment (*).
Corresponding β-actin expression for each sample is represented
below. M, 100-bp DNA ladder (Promega); B, negative control.