Differences in the gene expression profile (GEP) of patients with multiple myeloma (MM) can account for much of the heterogeneity of MM with respect to disease characteristics and clinical outcome. In view of the success of GEP in the nearly 250 patients on the Total Therapy 2 protocol who have been studied with this technique and the need to better understand the cellular and molecular biology of MM, including its microenvironment (ME) in order to develop treatments that effectively target tumor cells and the ME, we propose to establish a core facility to perform GEP on all newly diagnosed patients entering clinical trials in Dr. Barlogie's project, as well as patients on Total Therapy 2 experiencing disease relapse who enter salvage trials with novel agents (2003-35) and those experiencing disease relapse disease who enter clinical trials in Dr. Tricot's project. The primary objective of this Molecular Genetics core is to provide a highly specialized, molecular shared resource that will serve established research projects. This resource combines the facilities and expertise of the Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy of the Arkansas Cancer Research Center with those of the Cytogenetics Laboratory of the Arkansas Children's Hospital. The objective will be achieved through the following specific aims:
Specific Aim 1 : Assist in the conduct of research related to molecular genetics as proposed in each P01 project. Specifically, GEP, fluorescence in situ hybridization (FISH), and G-banded cytogenetics will be performed on patient samples and on samples from in vivo animal model studies and in vitro cell culture studies.
Specific Aim 2 : Maintain and correlate data from molecular genetic studies. Data mining and statistical analyses of GEP, FISH, and cytogenetics will be analyzed and developed into predictive models in collaboration with the biostatistics Core and Dr. Shaughnessy's project. Dr. Sanderson's project 5 seeks to understand how blocking heparan sulfate can alter the GEP of tumors growing in vivo, which could lead to development of new therapeutic targets.
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