CpG island hypermethylation is a frequent epigenetic event in cancer. We ha
ve recently developed an array-based method, called differential methylatio
n hybridization (DMH), allowing for a genome-wide screening of CpG island h
ypermethylation in breast cancer cell lines (T, H-M. Huang et al., Hum. Mol
. Genet., 8: 359-470, 1999), In the present study, DMH was applied to scree
n 28 paired primary breast tumor and normal samples and to determine whethe
r patterns of specific epigenetic alterations correlate with pathological p
arameters in the. patients analyzed, Amplicons, representing a pool of meth
ylated CpG DNA derived from these samples, were used as hybridization probe
s in an array panel containing 1104 CpG island tags. close to 9% of these t
ags exhibited extensive hypermethylation in the majority of breast tumors r
elative to their normal controls, whereas others had little or no detectabl
e changes. Pattern analysis in a subset of CpG island tags revealed that Cp
G island hypermethylation is associated with histological grades of breast
tumors. Poorly differentiated tumors appeared to exhibit more hypermethylat
ed CpG islands than their moderately or well-differentiated counterparts (P
= 0.041). This early finding lays the groundwork for a population-based DM
H. study and demonstrates the need to develop a database for examining larg
e-scale methylation data and for associating specific epigenetic signatures
with clinical parameters in breast cancer.