Steve M. Powell, MD
Molecular genetic analysis of gastric tumors
The Powell laboratory is focused on understanding gastric tumorigenesis through molecular genetic studies. They have comprehensively characterized many genetic loci that are frequently amplified or lost in our panel of xenografted and primary gastric cancers though CGH and allelic loss studies and continue to narrow in on the targets of alteration. They also are employing serial analysis of gene expression (SAGE) and cDNA microarray technology for the analysis of gene expression changes in gastric cancers. The lab already identified over 50 genes significantly altered in expression within gastric tumors compared to normal gastric tissue, some increased and some decreased. Many are gene products which are known to be involved in cell processes such as proliferation, cell cycle or apoptotic regulation, and adhesion or metastasis factors. Others gene products found to be significantly altered are novel to gastric cancer development and some even to cancer in general. Most intriguingly, several patterns of alterations could be traced to common signaling pathways such as that involving calcium regulators (S100A), beta-catenin, tissue metalloproteinases, and hepatoma derived growth factor. DARP32 and the novel t-DARP has been characterized to be overexpressed in the majority of gastric tumors. The prevalence of E-cadherin alterations in our "sporadic" gastric cancers occurred in approximately one third as it was found to be constitutionally involved in their familial diffuse gastric cancer cases.
The lab currently plans to further test the hypothesis that these cellular functions and signaling pathways are critical to gastric tumor development. They continue to narrow down regions of genetic loss in their panel of primary and xenografted gastric cancers and have shown 8p imbalance in these tumors to be associated with poor survival. Currently, the delineation of homozygous losses and significant regions of allelic loss are being mapped and biological significance explored. Common regions of amplification are additionally being sought, specifically at 20q. Additionally, the prognostic and biologic significance of gene alterations is being explored in gastric cancers.
They are also characterizing the loss of TFF1 in gastric cancers and determining the cause for its dysregulation in these gastric epithelial cells leading to neoplastic growth.