) Cancer is the second leading cause of death in the United States, accounting for nearly one quarter of total human mortality. Understanding the molecular changes that occur during the progression of human cancers could provide important data for prevention, early detection, diagnosis, and the development of optimal treatment protocols. The ability to produce a molecular fingerprint of each tumor may prove to be extremely important as histologically similar tumors may be the result of substantially different genetic changes. The Human Genome Project has provided important data and reagents that may serve as the basis for such an understanding. Analysis of the DNA sequence collected through the world-wide EST sequencing effort has allowed the identification of nearly 65,000 unique human transcripts and associated cDNA clones. Advances in technology also offer important new resources for the assessing the molecular state of a given tumor. cDNA microarraying is a recently developed technique that allows expression-level monitoring of as many as ten thousand individual transcripts on a single microscope slide. Laser capture microdissection allows the separation of tissue samples into unique cellular phenotypes. Used together with the cDNA and EST data that we now possess, these techniques should allow the identification of genes differentially expressed during tumor development and may allow the creation of novel technologies for evaluations of molecular alterations in tumors. The goal of this proposal is to use cDNA microarraying for the construction of molecular transcription profiles of tumors in a variety of tissues, focusing on breast, prostate, colon, lung, and ovary. Ultimately, we hope to develop a technique that will allow the rapid clinical analysis and characterization of human tumors through the microarray analysis of tissue-specific Reduced Expression Arrays.
|Agrawal, Deepak; Chen, Tingan; Irby, Rosalyn et al. (2002) Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst 94:513-21|
|Malek, Renae L; Irby, Rosalyn B; Guo, Qingbin M et al. (2002) Identification of Src transformation fingerprint in human colon cancer. Oncogene 21:7256-65|
|Hegde, P; Qi, R; Gaspard, R et al. (2001) Identification of tumor markers in models of human colorectal cancer using a 19,200-element complementary DNA microarray. Cancer Res 61:7792-7|
|Hegde, P; Qi, R; Abernathy, K et al. (2000) A concise guide to cDNA microarray analysis. Biotechniques 29:548-50, 552-4, 556 passim|