) The goal of this research is to use a first-generation DNA microarray system developed at Stanford to study gene expression patterns in normal and neoplastic human tissues. Rapidly growing knowledge of human expressed gene sequences will be applied to the problem of cancer by following the expression (at the mRNA level) of 10 to 20 thousand genes at once. Microarray hybridization will be used to study expression in a series of 60 human cancer cell lines already under intensive study by the NCI in connection with drug-susceptibility screening. Experience with these cell lines will aid in the design of experiments dealing with expression in samples of tumors and normal tissues provided by clinical collaborators. Arrangements have been made to obtain a large number of normal tissue samples from the genome anatomy project at NCI. Arrangements have also been made with clinical collaborators for preliminary surveys (ca. 100 samples) of lymphoma, breast cancer, colon cancer and leukemia. Suitably analyzed aggregate gene expression data should provide examples of genes whose expression, individually or as part of a complex pattern, is characteristic of particular types or sub-types of cancer. Information systems for acquisition, analysis and database storage of expression data will he put in place so that correlations of gene expression pattern with growth, physiology, disease state, drug susceptibility and eventually treatment outcome can be made. Mathematical algorithms for manipulating large datasets and testing similarity of expression patterns for many thousands of genes will be adapted or developed as needed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA077097-02
Application #
2796396
Study Section
Special Emphasis Panel (ZCA1-RLB-Y (O2))
Program Officer
Jacobson, James W
Project Start
1997-09-30
Project End
2000-09-29
Budget Start
1998-09-30
Budget End
1999-09-29
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Hogan, Gregory J; Brown, Patrick O; Herschlag, Daniel (2015) Evolutionary Conservation and Diversification of Puf RNA Binding Proteins and Their mRNA Targets. PLoS Biol 13:e1002307
Lovejoy, Alexander F; Riordan, Daniel P; Brown, Patrick O (2014) Transcriptome-wide mapping of pseudouridines: pseudouridine synthases modify specific mRNAs in S. cerevisiae. PLoS One 9:e110799
Holmes, Kristen J; Klass, Daniel M; Guiney, Evan L et al. (2013) Whi3, an S. cerevisiae RNA-binding protein, is a component of stress granules that regulates levels of its target mRNAs. PLoS One 8:e84060
Klass, Daniel M; Scheibe, Marion; Butter, Falk et al. (2013) Quantitative proteomic analysis reveals concurrent RNA-protein interactions and identifies new RNA-binding proteins in Saccharomyces cerevisiae. Genome Res 23:1028-38
Salzman, Julia; Klass, Daniel M; Brown, Patrick O (2013) Improved discovery of molecular interactions in genome-scale data with adaptive model-based normalization. PLoS One 8:e53930
Tsvetanova, Nikoleta G; Riordan, Daniel P; Brown, Patrick O (2012) The yeast Rab GTPase Ypt1 modulates unfolded protein response dynamics by regulating the stability of HAC1 RNA. PLoS Genet 8:e1002862
Casolari, Jason M; Thompson, Michael A; Salzman, Julia et al. (2012) Widespread mRNA association with cytoskeletal motor proteins and identification and dynamics of myosin-associated mRNAs in S. cerevisiae. PLoS One 7:e31912
del Alamo, Marta; Hogan, Daniel J; Pechmann, Sebastian et al. (2011) Defining the specificity of cotranslationally acting chaperones by systematic analysis of mRNAs associated with ribosome-nascent chain complexes. PLoS Biol 9:e1001100
Riordan, Daniel P; Herschlag, Daniel; Brown, Patrick O (2011) Identification of RNA recognition elements in the Saccharomyces cerevisiae transcriptome. Nucleic Acids Res 39:1501-9
Salzman, Julia; Marinelli, Robert J; Wang, Peter L et al. (2011) ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma. PLoS Biol 9:e1001156

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