Gene Expression Profiling of Normal Tiss

Basic Sciences

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Abstract

The non-specific nature of current cancer therapeutics, the lack of response in high-risk disease, and the severe, sometimes fatal, organ toxicities have driven cancer therapeutics towards rationally designed and specific molecularly targeted therapy. It is hoped that targeting genes expressed only in cancer, and not in normal tissue will minimize the side effects of therapy. These unique genes can also be used as tumor antigens for the development of vaccine-based immune therapies for childhood cancer (a primary interest of our branch of Pediatric Oncology Branch, NCI), which will reduce the risk of serious autoimmune manifestations. To achieve this aim, we are performing gene expression analysis on pediatric normal organ samples. The tissues were obtained from the Maryland Brain and Tissue Bank (http://medschool.umaryland.edu/btbank/). These samples include tissues from cerebrum, cerebellum, heart, lung, liver, pancreas, stomach, small intestine, large intestine, kidney, spleen, skeletal muscle, ovary, testes, ureter, uterus, bladder, adrenal gland, and prostate. The median age of the subjects from which the samples were obtained is 19yrs (range 2-40yrs), with a median post mortem interval (PMI) of 11hrs (range 4-19hrs). Information from the Bank suggests that the RNAs obtained from tissues within these PMIs are of good quality as judged by integrity of the ribosomal bands. The data generated by gene expression profiling will be collated and compared with the data generated from the malignant tissues. After publication, we will make the data available to outside investigators for searching via a web-based format.This data will be of utility for developing rationally designed molecularly targeted therapeutics in diseases such as cancer, as well as for exploring the functions of genes.