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2005 Scientific Report

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  • Mice
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  • Michigan
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Mouse models of kidney

Mouse models of kidney cancer In collaboration with VARI’s Bart Williams and Pam Swiatek, we have set up several mouse models for kidney tumors. These include conventional and conditional knock-outs for BHD, HRPT2, VHL, PTEN, and APC. For the latter three cases, we collaborated with Peter Igarashi of the University of Texas Southwestern Medical Center and obtained from him Ksp1.3/Cre transgenic mice expressing Cre recombinase exclusively in the kidney and developing GU tract, which can mediate epithelial-specific Cre/lox recombination in these tissues. We then crossed these mice with the APC-, VHL-, and PTEN-floxed mice. To date, we have completed the studies on APC conditional knock-outs, which give the phenotype of polycystic kidney disease and renal adenoma. We are currently characterizing the phenotypes of the other mice. In addition, we have established xenograft subcapsular models using five different RCC cell lines. The natural course of these models has been documented and studied by microarrary gene expression profiling. External Collaborators We have extensive collaborations with researchers and clinicians in the United States and overseas. Recent Publications Morris, M.R., D. Gentle, M. Abdulrahman, E.N. Maina, K. Gupta, R.E. Banks, M.S. Wiesener, T. Kishida, M. Yao, B. Teh, F. Latif, and E.R. Maher. In press. Tumor suppressor activity and epigenetic inactivation of hepatocyte growth factor activator inhibitor type 2 (HAI-2/SPINT2) in papillary and clear cell renal cell carcinoma. Cancer Research. Takahashi, M., X.J. Yang, S. McWhinney, N. Sano, C.H. Eng, S. Kagawa, B.T. Teh, and H. Kanayama. In press. cDNA microarray analysis assists in diagnosis of malignant intrarenal pheochromocytoma originally masquerading as a renal cell carcinoma. Journal of Medical Genetics. Tretiakova, M., M. Turkyilmaz, T. Grushko, M. Kocherginsky, C. Rubin, O. Olopade, B.T. Teh, and X.J. Yang. In press. Topoisomerase II[α] expression in Wilms tumors. Clinical Cancer Research. Wang, P., M.-H. Tan, C. Zhang, H. Morreau, and B.T. Teh. In press. HRPT2, a tumor suppressor gene for hyperparathyroidism-jaw tumor syndrome. Hormone and Metabolic Research. Yang, X.J., M.-H. Tan, H.L. Kim, J.A. Ditlev, M.W. Betten, C.E. Png, E.J. Kort, K. Futami, K.J. Dykema, K.A. Furge, M. Takahashi, H. Kanayama, P.H. Tan, B.S. Teh, C. Luan, et al. In press. A molecular classification of papillary renal cell carcinoma. Cancer Research. Cardinal, J., L. Bergman, N. Hayward, A. Sweet, J. Warner, L. Marks, D. Learoyd, T. Dwight, B. Robinson, M. Epstein, M. Smith, B.T. Teh, D. Cameron, and J. Prins. 2005. A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing. Journal of Medical Genetics 42(1): 69–74. Chuang, S.T., P. Chu, J. Sugimura, M.S. Tretiakova, V. Papavero, K. Wang, M.-H. Tan, F. Lin, B.T. Teh, and X.J. Yang. 2005. Overexpression of glutathione S-transferase α in clear cell renal cell carcinoma. American Journal of Clinical Pathology 123(3): 421–429. Lee, Youn-Soo, Alexander O. Vortmeyer, Irina A. Lubensky, Timothy W.A. Vogel, Barbara Ikejiri, Sophie Ferlicot, Gérard Benoît, Sophie Giraud, Edward H. Oldfield, W. Marston Linehan, Bin T. Teh, Stéphane Richard, and Zhengping Zhuang. 2005. Coexpression of erythropoietin and erythropoietin receptor in Von Hippel-Lindau disease–associated renal cysts and renal cell carcinoma. Clinical Cancer Research 11(3): 1059–1064. Qian, Chao-Nan, Jared Knol, Peter Igarashi, Fangmin Lin, Uko Zylstra, Bin Tean Teh, and Bart O. Williams. 2005. Cystic renal neoplasia following conditional inactivation of Apc in mouse renal tubular epithelium. Journal of Biological Chemistry 280(5): 3938–3945. Robertson, Scott A., Jacqueline Schoumans, Brendan D. Looyenga, Jason A. Yuhas, Cassandra R. Zylstra, Julie M. Koeman, Pamela J. Swiatek, Bin T. Teh, and Bart O. Williams. 2005. Spectral 46

karyotyping of sarcomas and fibroblasts derived from Ink4a/Arf-deficient mice reveals chromosomal instability in vitro. International Journal of Oncology 26(3): 629–634. Rogers, C., M.-H. Tan, and B.T. Teh. 2005. Gene expression profiling of renal cell carcinoma and clinical implications. Urology 65(2): 231–237. Schoumans, Jacqueline, Ann Nordgren, Claudia Ruivenkamp, Karen Brøndum-Nielsen, Bin Tean Teh, Göran Annéren, Eva Holmberg, Magnus Nordenskjöld, and Britt-Marie Anderlid. 2005. Genome-wide screening using array-CGH does not reveal microdeletions/microduplications in children with Kabuki syndrome. European Journal of Human Genetics 13(2): 260–263. Takahashi, Masayuki, Veronica Papavero, Jason Yuhas, Eric Kort, Hiro-omi Kanayama, Susumu Kagawa, R.C. Baxter, Ximing J. Yang, Steven G. Gray, and Bin T. Teh. 2005. Altered expression of members of the IGF-axis in clear cell renal cell carcinoma. International Journal of Oncology 26(4): 923–931. Akervall, Jan, Xiang Guo, Chao-Nan Qian, Jacqueline Schoumans, Brandon Leeser, Eric Kort, Andrew Cole, James Resau, Carol Bradford, Thomas Carey, Johan Wennerberg, Harald Anderson, Jan Tennvall, and Bin T. Teh. 2004. Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients. Clinical Cancer Research 10(24): 8204–8213. Atkins, Michael B., David E. Avigan, Ronald M. Bukowski, Richard W. Childs, Janice P. Dutcher, Tim G. Eisen, Robert A. Figlin, James H. Finke, Robert C. Flanigan, Daniel J. George, S. Nahum Goldberg, Michael S. Gordon, Othon Iliopoulos, William G. Kaelin, Jr., W. Marston Linehan, et al. 2004. Innovations and challenges in renal cancer: consensus statement. Clinical Cancer Research 10(18, Pt.2): 6277S–6281S. Calender, A., C. Morrison, P. Komminoth, J.Y. Scaoazec, K. Sweet, and B.T. Teh. 2004. Multiple endocrine neoplasia type 1. In Pathology and Genetics of Tumours of the Endocrine Organs, DeLellis, Heitz, Lloyd, and Eng, eds. WHO Classification of Tumours series, Vol. 8. Lyon, France: IARC Press, pp. 218–227. Furge, Kyle A., Kerry A. Lucas, Masayuki Takahashi, Jun Sugimura, Eric J. Kort, Hiro-omi Kanayama, Susumu Kagawa, Philip Hoekstra, John Curry, Ximing J. Yang, and Bin T. Teh. 2004. Robust classification of renal cell carcinoma based on gene expression data and predicted cytogenetic profiles. Cancer Research 64(12): 4117–4121. Haven, Carola J., Viive M. Howell, Paul H.C. Eilers, Robert Dunne, Masayuki Takahashi, Marjo van Puijenbroek, Kyle Furge, Job Kievit, Min-Han Tan, Gert Jan Fleuren, Bruce G. Robinson, Leigh W. Delbridge, Jeanette Philips, Anne E. Nelson, Ulf Krause, et al. 2004. Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype. Cancer Research 64(20): 7405–7411. Lindvall, Charlotta, Kyle Furge, Magnus Björkholm, Xiang Guo, Brian Haab, Elisabeth Blennow, Magnus Nordenskjöld, and Bin Tean Teh. 2004. Combined genetic and transcriptional profiling of acute myeloid leukemia with normal and complex karyotypes. Haematologica 89(9): 1072–1081. Luccio-Camelo, Douglas C., Karina N. Une, Rafael E.S. Ferreira, Sok Kean Khoo, Radoslav Nickolov, Marcello D. Bronstein, Mario Vaisman, Bin Tean Teh, Lawrence A. Frohman, Berenice B. Mendonca, and Monica R. Gadelha. 2004. A meiotic recombination in a new isolated familial somatotropinoma kindred. European Journal of Endocrinology 150(5): 643–648. Marsh, Deborah J., Hans Morreau, and Bin T. Teh. 2004. HRPT2 and parathyroid cancer. Lancet Oncology 5(2): 78. Morrison, C., K. Sweet, and B.T. Teh. 2004. Hyperthyroidism-jaw tumor syndrome. In Pathology and Genetics of Tumours of the Endocrine Organs, DeLellis, Heitz, Lloyd, and Eng, eds. WHO Classification of Tumours series, Vol. 8. Lyon, France: IARC Press, pp. 228–237. Patton, Kurt T., Maria S. Tretiakova, Jorge L. Yao, Veronica Papavero, Lei Huo, Brian P. Adley, Guan Wu, Jiaoti Huang, Michael R. Pins, Bin T. Teh, and Ximing J. Yang. 2004. Expression of RON proto-oncogene in renal oncocytoma and chromophobe renal cell carcinoma. American Journal of Surgical Pathology 28(8): 1045–1050. 47

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