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2002 Scientific Report

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Laboratory of Cancer

Laboratory of Cancer Genetics Bin T. Teh, M.D., Ph.D. Dr. Teh obtained his M.D. from the University of Queensland, Australia, in 1992, and his Ph.D. from the Karolinska Institute, Sweden, in 1997. Before joining the Van Andel Research Institute, he was an Associate Professor of medical genetics at the Karolinska Institute. Dr. Teh joined VARI as a Senior Scientific Investigator in January 2000. Staff Miles Chao-Nan Qian, M.D., Ph.D. Libing Song, M.D.. Ph.D. Jun Sugimura, M.D., Ph.D. Jindong Chen, Ph.D. Sok Kean Khoo, Ph.D. David Petillo, Ph.D. Chun Zhang, Ph.D. Eric Kort, M.S. Olga Motorna, B.S. Jason Yuhas, B.S. Laboratory Members Visiting Scientists Charlotta Lindvall, M.D., Ph.D. Joe Chien-Chung Chou, M.D. Carola Haven, M.D. Kanthimathi M.S., Ph.D. Vivve Howell, M.S. Jacqueline Schoumans, M.S. Students Katherine Kahnoski Todd Lavery Casey Madura Grace Miguel Radoslav Nickolov Sarah Scolon Research Projects Cancer formation is a multistep process that results from genetic instability in the cells. At the molecular level it is characterized by multiple alterations in genes that play key regulatory roles in various cellular functions. Our laboratory is interested in identifying and studying these genetic alterations in both hereditary cancers and their sporadic counterparts. Currently we are focusing on three types of tumors: kidney tumors, nasopharyngeal carcinoma, and endocrine (hormone-secreting) tumors. We have close and extensive collaborations with researchers and clinicians at hospitals and universities in this country and overseas. We have initiated a program to study hereditary kidney cancer and to date we have identified several families with the disease. Both cytogenetic and molecular studies have been performed to elucidate this cancer’s genetic basis. We have identified a family with a chromosome 3 translocation and currently we are trying to clone the breakpoint genes. We also have mapped the gene for Birt-Hogg-Dubé syndrome, a hereditary cancer, to chromosome 17. This autosomal dominant disease is characterized by skin and kidney tumors and cysts in the lung. In addition, we have been working on another hereditary disease, hyperparathyroidism–jaw tumor syndrome, which is characterized by parathyroid tumors, jaw tumors, and kidney cysts and tumors. In sporadic kidney tumors, we have studied the gene expression profiles of renal cell carcinoma and correlated them with clinical outcomes. We have also characterized the biological profiles of kidney tumors having different histopathologies, including pediatric kidney tumors (Wilms tumor). We confirm our microarray findings by both real-time polymerase chain reaction (RT-PCR) and immunohistochemical studies on kidney cancer tissue arrays. Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and Southeast Asia. We are undertaking studies to identify cancer-related genes in NPC cell lines and primary tumors and to correlate their expression with clinical parameters. In endocrine or hormone-secreting tumors, we continue to work on multiple endocrine neoplasia type 1 and have found new mutations in new MEN1 families. We are currently focusing on the mapping of the gene for familial acromegaly, a hereditary condition characterized by tumors in the pituitary glands that secrete growth hormone. In addition to carrying out these research projects, our laboratory has provided core sequencing and cytogenetic services to the Institute. To date over 15,000 sequences have been performed. We have also performed cytogenetics studies including FISH, conventional CGH, and SKY in collaboration with internal and external researchers. 43

External Collaborators We have extensive collaborations with researchers and clinicians from this country and overseas. Publications Dwight, T., S. Kytola, B.T. Teh, G. Theodosopoulos, A.L. Richardson, J. Philips, S. Twigg, L. Delbridge, D.J. Marsh, A.E. Nelson, C. Larsson, and B.G. Robinson. 2002. Genetic analysis of lithium-associated parathyroid tumors. European Journal of Endocrinology 146(5): 619–627. Dwight, T., A.E. Nelson, D.J. Marsh, B.T. Teh, C. Larsson, and B.G. Robinson. In press. Parathyroid tumorigenesis in association with primary hyperparathyroidism. Current Opinion in Endocrinology and Diabetes. Dwight, T., A.E. Nelson, G. Theodosopoulos, A.L. Richardson, D.L. Learoyd, J. Philips, L. Delbridge, J. Zedenius, B.T. Teh, C. Larsson, D. Marsh, and B.G. Robinson. In press. Independent genetic events associated with the development of multiple parathyroid tumors in patients with primary hyperparathyroidism. American Journal of Pathology. Haddad, Ramsi, Kyle A. Furge, Jeremy C. Miller, Brian B. Haab, J. Schoumans, B.T. Teh, L. Barr, and Craig P. Webb. In press. Genomic profiling and cDNA microarray analysis of human colon adenocarcinoma and associated intraperitoneal metastases reveals consistent cytogenetic and transcriptional aberrations associated with progression of multiple metastases. Applied Genomics and Proteomics. Lui, Weng-Onn, Jindong Chen, Sven Glasker, Bernhad U. Bender, Casey Madura, Sok Kean Khoo, Eric Kort, Catharina Larsson, Harmut P.H. Neumann, and Bin T. Teh. 2002. Selective loss of chromosome 11 in pheochromocytomas associated with the VHL syndrome. Oncogene 21(7): 1117–1122. Perrier, N.D., A. Villablanca, C. Larsson, M. Wong, B.T. Teh, and O.H. Clark. In press. Genetic screening for MEN1 in “familial isolated hyperparathyroidism.” World Journal of Surgery. Qian, Chao-Nan, Xiang Guo, Brian Cao, Eric Kort, Chong-Chou Lee, Jindong Chen, Ling-Mei Wang, Wei-Yuan Mai, Hua-Qing Min, Ming-Huang Hong, George F. Vande Woude, James H. Resau, and Bin T. Teh. 2002. Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma. Cancer Research 62(2): 589–596. Takahashi, M., R. Kahnoski, D. Gross, D. Nicol, and B.T. Teh. 2002. Familial adult renal neoplasia. Journal of Medical Genetics 39(1): 1–5. Villablanca, Andrea, Filip Farnebo, Bin T. Teh, Lars-Ove Farnebo, Anders Höög, and Catharina Larsson. 2002. Genetic and clinical characterization of sporadic cystic parathyroid tumours. Clinical Endocrinology 56(2): 261–269. From left to right: Teh, Qian, Chen, Yuhas, Motorna, Khoo, Song, Petillo, Zhang, Sugimura 44

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