Identifying genes progressively silenced in preneoplastic and neoplastic liver tissues

Abstract

High-throughput genomic technologies are increasingly being used to identify therapeutic targets and risk factors for specific diseases. Using 116 independent liver samples, we identified 793 probe sets that demonstrated a significant association in the frequency of absent calls as tissues progressed from normal to pre-neoplastic to neoplastic, followed by a bioinformatic approach which identified that 78.9% of the significant probe sets contained at least one CpG island in the gene promoter region compared with 58.9% of the remaining genes examined. Our results indicate that further high-throughput methylation studies to more fully characterize molecular events involved in hepatocarcinogenesis are warranted.

Figure 1

Molecular and cellular functions corresponding to the 793 significant probe sets and sorted by p-value according to ingenuity pathway analysis software (see online version for colours)

Figure 2

Agglomerative hierarchical clustering using Ward’s method on the 4650 probe sets retained after filtering. Labels indicate underlying tissue of origin as N = normal, c = pre-neoplastic tissue (HCV + cirrhosis) and H = neoplastic tissue (HCV + HCC)