Interrogation of WNT Signaling Pathway Activation in Adrenocortical Carcinoma by Transcriptome Profiling
TJ Giordano, R Kuick, DG Thomas, T Else, M Vinco, D Sanders, G Hammer. University of Michigan, Ann Arbor, MI
Background: WNT signaling pathway activation is a hallmark of colon cancer and common to many tumors types, including those of the adrenal cortex.
Design: To assess the relative significance of WNT activation in adrenocortical carcinoma (ACC), we combined genome-wide gene expression profiles derived from DNA microarray analysis of a large cohort of tumors with molecular markers of WNT activation. Specifically, we annotated the ACCs by -catenin immunohistochemistry and CTNNB1 mutational analysis.
Results: Using this approach, we identified, using p<0.01 and fold change >1.5 as selection criteria, a list of 811 unique differentially expressed genes in ACC related to WNT pathway activation. Bioinformatic evaluation of these genes revealed an overrepresentation of genes related to cell adhesion, the WNT signaling pathway, and genes with LEF1 promoter binding sites. Kaplan-Meier survival analysis revealed that ACCs with WNT pathway activation were associated with a slightly poorer outcome.
Conclusions: Collectively, these results indicate that WNT signaling pathway activation is a biologically significant event in approximately one-third of ACCs, a finding with pathogenetic and therapeutic implications.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 239, Tuesday Morning