Altered genome
methylation is a hallmark of human malignancies.
In this study, high-throughput analyses of concordant gene
methylation and expression events were performed for 91 human prostate
specimens, including prostate tumor (T), matched normal adjacent to tumor (AT),
and organ donor (OD). Methylated DNA in genomic DNA was immunoprecipitated with
anti-methylcytidine antibodies and detected by Affymetrix human whole genome
SNP 6.0 chips. Among the methylated CpG islands, 11,481 islands were found
located in the promoter and exon 1 regions of 9295 genes. Genes (7641) were
methylated frequently across OD, AT, and T samples, whereas 239 genes were
differentially methylated in only T and 785 genes in both AT and T but not OD.
Genes with promoter methylation and concordantly suppressed expression were
identified. Pathway analysis suggested that many of the methylated genes in T
and AT are involved in cell growth and mitogenesis. Classification analysis of
the differentially methylated genes in T or OD produced a specificity of 89.4%
and a sensitivity of 85.7%. The T and AT groups, however, were only slightly
separated by the prediction analysis, indicating a strong field effect. A gene
methylation prediction model was shown to predict prostate cancer relapse with
sensitivity of 80.0% and specificity of 85.0%. These results suggest
methylation patterns useful in predicting clinical outcomes of prostate cancer.
Written
by:
Luo JH, Ding Y, Chen R, Michalopoulos G, Nelson J, Tseng G, Yu YP.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Luo JH, Ding Y, Chen R, Michalopoulos G, Nelson J, Tseng G, Yu YP.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Reference: Am J Pathol. 2013 Jun;182(6):2028-36.
doi: 10.1016/j.ajpath.2013.02.040
doi: 10.1016/j.ajpath.2013.02.040
