This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buckhaults, P. Articles by Shih, I.-M. Search for Related Content PubMed PubMed Citation Articles by Buckhaults, P. Articles by Shih, I.-M.

Identifying Tumor Origin Using a Gene Expression-based Classification Map¹

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins [P. B., T-L. W., S. S., A. B., V. E. V.] and The Department of Pathology [Z. Z., Y-C. C., R. H. H., I-M. S.], Johns Hopkins Medical Institutions, Baltimore, Maryland 21231; The National Cancer Institute, Frederick, Maryland [B. St. C.]; National Institute on Aging, Baltimore, Maryland [P. J. M.]; and Dana-Farber Cancer Institute, Boston, Massachusetts [K. P.]

Identifying the primary site in cases of metastatic carcinoma of unknown origin has profound clinical importance in managing cancer patients. Although transcriptional profiling promises molecular solutions to this clinical challenge, simpler and more reliable methods for this purpose are needed. A training set of 11 serial analysis of gene expression (SAGE) libraries was analyzed using a combination of supervised and unsupervised computational methods to select a small group of candidate genes with maximal power to discriminate carcinomas of different tissue origins. Quantitative real-time PCR was used to measure their expression levels in an independent validation set of 62 samples of ovarian, breast, colon, and pancreatic adenocarcinomas and normal ovarian surface epithelial controls. The diagnostic power of this set of genes was evaluated using unsupervised cluster analysis methods. From the training set of 21,321 unique SAGE transcript tags derived from 11 libraries, five genes were identified with expression patterns that distinguished four types of adenocarcinomas. Quantitative real-time PCR expression data obtained from the validation set clustered tumor samples in an unsupervised manner, generating a self-organized map with distinctive tumor site-specific domains. Eighty-one percent (50 of 62) of the carcinomas were correctly allocated in their corresponding diagnostic regions. Metastases clustered tightly with their corresponding primary tumors. A classification map diagnostic of tumor types was generated based on expression patterns of five genes selected from the SAGE database. This expression map analysis may provide a reliable and practical approach to determine tumor type in cases of metastatic carcinoma of clinically unknown origin.

This article has been cited by other articles:

				J.-H. Choi, J. T. Park, B. Davidson, P. J. Morin, I.-M. Shih, and T.-L. Wang Jagged-1 and Notch3 Juxtacrine Loop Regulates Ovarian Tumor Growth and Adhesion Cancer Res., July 15, 2008; 68(14): 5716 - 5723. [Abstract] [Full Text] [PDF]

				J. J.-C. Sheu, J. H. Choi, I. Yildiz, F.-J. Tsai, Y. Shaul, T.-L. Wang, and I.-M. Shih The Roles of Human Sucrose Nonfermenting Protein 2 Homologue in the Tumor-Promoting Functions of Rsf-1 Cancer Res., June 1, 2008; 68(11): 4050 - 4057. [Abstract] [Full Text] [PDF]

				S. Yeasmin, K. Nakayama, M. Ishibashi, A. Katagiri, K. Iida, I. N. Purwana, N. Nakayama, and K. Miyazaki Expression of the Bric-a-Brac Tramtrack Broad Complex Protein NAC-1 in Cervical Carcinomas Seems to Correlate with Poorer Prognosis Clin. Cancer Res., March 15, 2008; 14(6): 1686 - 1691. [Abstract] [Full Text] [PDF]

				C. I. Dumur, M. Lyons-Weiler, C. Sciulli, C. T. Garrett, I. Schrijver, T. K. Holley, J. Rodriguez-Paris, J. R. Pollack, J. L. Zehnder, M. Price, et al. Interlaboratory Performance of a Microarray-Based Gene Expression Test to Determine Tissue of Origin in Poorly Differentiated and Undifferentiated Cancers J. Mol. Diagn., January 1, 2008; 10(1): 67 - 77. [Abstract] [Full Text] [PDF]

				K. Nakayama, N. Nakayama, T.-L. Wang, and I.-M. Shih NAC-1 Controls Cell Growth and Survival by Repressing Transcription of Gadd45GIP1, a Candidate Tumor Suppressor Cancer Res., September 1, 2007; 67(17): 8058 - 8064. [Abstract] [Full Text] [PDF]

				D. Talantov, J. Baden, T. Jatkoe, K. Hahn, J. Yu, Y. Rajpurohit, Y. Jiang, C. Choi, J. S. Ross, D. Atkins, et al. A Quantitative Reverse Transcriptase-Polymerase Chain Reaction Assay to Identify Metastatic Carcinoma Tissue of Origin J. Mol. Diagn., July 1, 2006; 8(3): 320 - 329. [Abstract] [Full Text] [PDF]

				J. T. Park, M. Li, K. Nakayama, T.-L. Mao, B. Davidson, Z. Zhang, R. J. Kurman, C. G. Eberhart, I.-M. Shih, and T.-L. Wang Notch3 gene amplification in ovarian cancer. Cancer Res., June 15, 2006; 66(12): 6312 - 6318. [Abstract] [Full Text] [PDF]

				I.-M. Shih, J. J.-C. Sheu, A. Santillan, K. Nakayama, M. J. Yen, R. E. Bristow, R. Vang, G. Parmigiani, R. J. Kurman, C. G. Trope, et al. Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma PNAS, September 27, 2005; 102(39): 14004 - 14009. [Abstract] [Full Text] [PDF]

				D. A. Smirnov, D. R. Zweitzig, B. W. Foulk, M. C. Miller, G. V. Doyle, K. J. Pienta, N. J. Meropol, L. M. Weiner, S. J. Cohen, J. G. Moreno, et al. Global Gene Expression Profiling of Circulating Tumor Cells Cancer Res., June 15, 2005; 65(12): 4993 - 4997. [Abstract] [Full Text] [PDF]

				R. W. Tothill, A. Kowalczyk, D. Rischin, A. Bousioutas, I. Haviv, R. K. van Laar, P. M. Waring, J. Zalcberg, R. Ward, A. V. Biankin, et al. An Expression-Based Site of Origin Diagnostic Method Designed for Clinical Application to Cancer of Unknown Origin Cancer Res., May 15, 2005; 65(10): 4031 - 4040. [Abstract] [Full Text] [PDF]

				G. Pohl, C.-L. Ho, R. J. Kurman, R. Bristow, T.-L. Wang, and I.-M. Shih Inactivation of the Mitogen-Activated Protein Kinase Pathway as a Potential Target-Based Therapy in Ovarian Serous Tumors with KRAS or BRAF Mutations Cancer Res., March 1, 2005; 65(5): 1994 - 2000. [Abstract] [Full Text] [PDF]

				R. Huang, Y. Lin, Q. Shi, L. Flowers, S. Ramachandran, I. R. Horowitz, S. Parthasarathy, and R.-P. Huang Enhanced Protein Profiling Arrays with ELISA-Based Amplification for High-Throughput Molecular Changes of Tumor Patients' Plasma Clin. Cancer Res., January 15, 2004; 10(2): 598 - 609. [Abstract] [Full Text] [PDF]

				R. D. Cardiff, A. Rosner, M. A. Hogarth, J. J. Galvez, A. D. Borowsky, and J. P. Gregg Validation: The New Challenge for Pathology Toxicol Pathol, January 1, 2004; 32(1_suppl): 31 - 39. [Abstract] [PDF]