11 months ago

2007 Scientific Report

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VARI | 2007 Computational analysis of gene expression data derived from papillary RCC revealed that a transcriptional signature indicative of MYC pathway activation was present in high-grade papillary RCC, but not other high-grade RCCs. Predictions of chromosomal gains and losses were also generated from the gene expression data, and it was demonstrated that the presence of the MYC signature was coincident with a predicted amplification of chromosome 8q. Because the c-MYC gene maps to chromosome 8q, a computational model was developed such that amplification of chromosome 8q occurs in the high-grade papillary tumors, which leads to c-MYC overexpression and activation of the MYC pathway. The importance of MYC activation was confirmed by both pharmacological and siRNA inhibition of active MYC signaling in a cell line model of high-grade papillary RCC. These results highlight the effectiveness of using gene expression profiling data to build integrative computational models of tumor development and progression. 25 From left: Dykema, Furge Recent Publications Furge, Kyle A., Jindong Chen, Julie Koeman, Pamela Swiatek, Karl Dykema, Kseniji Lucin, Richard Kahnoski, Ximing J. Yang, and Bin Tean Teh. 2007. Detection of DNA copy number changes and oncogenic signaling abnormalities from gene expression data reveals MYC activation in high-grade papillary renal cell carcinoma. Cancer Research 67(7): 3171–3176. Furge, K.A., M.H. Tan, K. Dykema, E. Kort, W. Stadler, X. Yao, M. Zhou, and B.T. Teh. 2007. Identification of deregulated oncogenic pathways in renal cell carcinoma: an integrated oncogenomic approach based on gene expression profiling. Oncogene 26(9): 1346–1350. Furge, Kyle A., Eric J. Kort, Ximing J. Yang, Walter M. Stadler, Hyung Kim, and Bin Tean Teh. 2006. Gene expression profiling in kidney cancer: combining differential expression and chromosomal and pathway analyses. Clinical Genitourinary Cancer 5(3): 227–231. Yang, Ximing J., Jun Sugimura, Kristian T. Schafernak, Maria S. Tretiakova, Misop Han, Nicholas J. Vogelzang, Kyle Furge, and Bin Tean Teh. 2006. Classification of renal neoplasms based on molecular signatures. Journal of Urology 175(6): 2302–2306.

Van Andel Research Institute | Scientific Report Brian B. Haab, Ph.D. Laboratory of Cancer Immunodiagnostics 26 Dr. Haab obtained his Ph.D. in chemistry from the University of California at Berkeley in 1998. He then served as a postdoctoral fellow in the laboratory of Patrick Brown in the Department of Biochemistry at Stanford University. Dr. Haab joined VARI as a Special Program Investigator in May 2000 and became a Scientific Investigator in 2004. Staff Laboratory Staff Songming Chen, Ph.D. Michael Shafer, Ph.D. Yi-Mi Wu, Ph.D. Derek Bergsma, B.S. Sara Forrester, B.S. Thomas LaRoche, B.S. Tingting Yue, B.S. Alex Turner Students Krysta Collins Jennifer Lunger Devin Mistry Visiting Scientist Rasmus Lundquist

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