11 months ago

2008 Scientific Report

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Van Andel Research

Van Andel Research Institute | Scientific Report 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. From left: Furge, Johnson, Klomp, Dykema Recent Publications Camparo, P., V. Vasiliu, V. Molinié, J. Couturier, K. Dykema, D. Petillo, K.A. Furge, E.M. Comperat, M. Laé, R. Bouvier, L. Boccon-Gibbod, Y. Denoux, S. Ferlicot, E. Forest, G. Fromont, et al. In press. Renal translocation carcinomas: clinicopathological, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature. American Journal of Surgical Pathology. Ding, Yan, Elissa A. Boguslawski, Bree D. Berghuis, John J. Young, Zhongfa Zhang, Kim Hardy, Kyle Furge, Eric Kort, Arthur E. Frankel, Rick V. Hay, James H. Resau, and Nicholas S. Duesbery. 2008. Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma. Molecular Cancer Therapeutics 7(3): 648–658. Gao, ChongFeng, Kyle Furge, Julie Koeman, Karl Dykema, Yanli Su, Mary Lou Cutler, Adam Werts, Pete Haak, and George F. Vande Woude. 2007. Chromosome instability, chromosome transcriptome, and clonal evolution of tumor cell populations. Proceedings of the National Academy of Sciences U.S.A. 104(21): 8995–9000. 24

VARI | 2008 Brian B. Haab, Ph.D. Laboratory of Cancer Immunodiagnostics 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, became a Scientific Investigator in 2004, and was promoted to Senior Scientific Investigator in 2007. Staff Students Visiting Scientists Songming Chen, Ph.D. Yi-Mi Wu, Ph.D. Derek Bergsma, B.S. Sara Forrester, B.S. Andrew Porter, B.S. Tingting Yue, B.S. Alex Turner Krysta Collins Carrie Fiebig Adam Granger Lee Heeringa Kevin Maupin Randi VanOcker David Nowack, Ph.D. 25

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