Genome-wide expression profiling of normal tissue may facilitate our understanding of the etiology of diseased organs and augment the development of new targeted therapeutics. Wehave developed a high-density gene expression database of 18,927 unique genes for 158 normal human samples from 19 different organs of 30 different individuals using DNA microarrays. We report four main findings. First, despite very diverse sample parameters (e.g., age, ethnicity, sex, and postmortem interval), the expression profiles belonging to the same organs cluster together, demonstrating internal stability of the database. Second, the gene expression profiles reflect major organ-specific functions on the molecular level, indicating consistency of our database with known biology. Third, we demonstrate that any small (i.e., n 100), randomly selected subset of genes can approximately reproduce the hierarchical clustering of the full data set, suggesting that the observed differential expression of more than 90% of the probed genes is of biological origin. Fourth, we demonstrate a potential application of this database to cancer research by identifying 19 tumor-specific genes in neuroblastoma. The selected genes are relatively un derexpressed in all of the organs examined and belong to therapeutically relevant pathways, making them potential novel diagnostic markers and targets for therapy. We expect this database 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. Our paper was published in Genome Research (see below) and all the data is available on the web http://home.ccr.cancer.gov/oncology/oncogenomics/. The database has been extensively utilized by both industry and academia and has over 2,000 registered users. Recently we have begun to perform both whole exon expression profiling and microRNA profiling of normal tissues. While most conventional genes encode proteins to carry out their biological functions, the recently discovered class of genes transcribing small non-coding RNAs, namely microRNAs, was found to play important regulatory roles in normal development and physiology in plants and animals. Mature microRNAs are 20-22 nucleotides molecules that can regulate gene expression through RNA interference effecter complex (RISC) mediated mRNA degradation and translational suppression via complimentary pairing to predominantly-untranslated region (3'-UTR) of their targeted messenger RNAs. Increasing number of studies has demonstrated a perturbation of the normal expression patterns of microRNAs in many human cancers. We will compare these microRNA expression profiles from normal tissues with that of pediatric malignant tissues to identify potential biomarkers and targets for therapy. It will increase our understating of the role of microRNAs in the tumorigenic process for these cancers. We are also adding other normal organs to this database and keeping it updated for other investigators. Our entire normal tissue data has been released to the public. The data offers a unique tool that all cancer scientists and clinical researchers can use to better define potential drug targets and anticipate where else in the body a targeted agent might be expressed. The database may also help to elucidate gene-gene interactions and pathways useful not only to cancer biologists, but also to those developing new drugs for a wide range of diseases such as heart disease and autoimmune disorders. It has over 2000 registered users and is of a broad interest at NIH and to extramural investigators (http://home.ccr.cancer.gov/oncology/oncogenomics).Genome-wide expression profiling of normal tissue may facilitate our understanding of the etiology of diseased organs and augment the development of new targeted therapeutics. Wehave developed a high-density gene expression database of 18,927 unique genes for 158 normal human samples from 19 different organs of 30 different individuals using DNA microarrays. We report four main findings. First, despite very diverse sample parameters (e.g., age, ethnicity, sex, and postmortem interval), the expression profiles belonging to the same organs cluster together, demonstrating internal stability of the database. Second, the gene expression profiles reflect major organ-specific functions on the molecular level, indicating consistency of our database with known biology. Third, we demonstrate that any small (i.e., n 100), randomly selected subset of genes can approximately reproduce the hierarchical clustering of the full data set, suggesting that the observed differential expression of more than 90% of the probed genes is of biological origin. Fourth, we demonstrate a potential application of this database to cancer research by identifying 19 tumor-specific genes in neuroblastoma. The selected genes are relatively un derexpressed in all of the organs examined and belong to therapeutically relevant pathways, making them potential novel diagnostic markers and targets for therapy. We expect this database 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. Our paper was published in Genome Research (see below) and all the data is available on the web http://home.ccr.cancer.gov/oncology/oncogenomics/. The database has been extensively utilized by both industry and academia and has over 2,000 registered users. Recently we have begun to perform both whole exon expression profiling and microRNA profiling of normal tissues. While most conventional genes encode proteins to carry out their biological functions, the recently discovered class of genes transcribing small non-coding RNAs, namely microRNAs, was found to play important regulatory roles in normal development and physiology in plants and animals. Mature microRNAs are 20-22 nucleotides molecules that can regulate gene expression through RNA interference effecter complex (RISC) mediated mRNA degradation and translational suppression via complimentary pairing to predominantly-untranslated region (3'-UTR) of their targeted messenger RNAs. Increasing number of studies has demonstrated a perturbation of the normal expression patterns of microRNAs in many human cancers. We will compare these microRNA expression profiles from normal tissues with that of pediatric malignant tissues to identify potential biomarkers and targets for therapy. It will increase our understating of the role of microRNAs in the tumorigenic process for these cancers. We are also adding other normal organs to this database and keeping it updated for other investigators. Our entire normal tissue data has been released to the public. The data offers a unique tool that all cancer scientists and clinical researchers can use to better define potential drug targets and anticipate where else in the body a targeted agent might be expressed. The database may also help to elucidate gene-gene interactions and pathways useful not only to cancer biologists, but also to those developing new drugs for a wide range of diseases such as heart disease and autoimmune disorders. It has over 2000 registered [summary truncated at 7800 characters]
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