This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Shridhar, V. Articles by Smith, D. I. Search for Related Content PubMed PubMed Citation Articles by Shridhar, V. Articles by Smith, D. I.

Identification of Underexpressed Genes in Early- and Late-Stage Primary Ovarian Tumors by Suppression Subtraction Hybridization¹

Department of Experimental Pathology, Division of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905 [V. S., J. C., J. S., R. A., D. I. S.]; Millennium Predictive Medicine, Cambridge, Massachusetts 02139 [A. S., S. K., J. Li.]; and Corning, Acton, Massachusetts 01720 [J. Le.]

To identify novel tumor suppressor genes involved in ovarian carcinogenesis, we generated four down-regulated suppression subtraction cDNA libraries from two early-stage (stage I/II) and two late-stage (stage III) primary ovarian tumors, each subtracted against cDNAs derived from normal ovarian epithelial cell brushings. Approximately 600–700 distinct clones were sequenced from each library. Comparison of down-regulated clones obtained from early- and late-stage tumors revealed genes that were unique to each library which suggested tumor-specific differences. We found 45 down-regulated genes that were common in all four libraries. We also identified several genes, the role of which in tumor development has yet to be elucidated, in addition to several under expressed genes, the potential role of which in carcinogenesis has been described previously (Bagnoli et al., Oncogene, 19: 4754–4763, 2000; Yu et al., Proc. Natl. Acad. Sci. USA, 96: 214–219, 1999; Mok et al., Oncogene, 12: 1895–1901, 1996). The differential expression of a subset of these genes was confirmed by semiquantitative reverse transcription-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as control in a panel of 15 stage I and 15 stage III tumors of mixed histological subtypes. Chromosomal sorting of library sequences revealed that several of the genes mapped to known regions of deletion in ovarian cancer. Loss of heterozygosity (LOH) analysis revealed multiple genomic regions with a high frequency of loss in both early- and late-stage tumors. To determine whether loss of expression of some of the genes corresponds to loss of an allele by LOH, we used a microsatellite marker for one of the novel genes on 8q and have shown that loss of expression of this novel gene correlates with loss of an allele by LOH. In conclusion, our analysis has identified down-regulated genes, which map to known as well as novel regions of deletions and may represent potential candidate tumor suppressor genes involved in ovarian cancer.

This article has been cited by other articles:

				G. Zupkovitz, J. Tischler, M. Posch, I. Sadzak, K. Ramsauer, G. Egger, R. Grausenburger, N. Schweifer, S. Chiocca, T. Decker, et al. Negative and Positive Regulation of Gene Expression by Mouse Histone Deacetylase 1 Mol. Cell. Biol., November 1, 2006; 26(21): 7913 - 7928. [Abstract] [Full Text] [PDF]

				S. Grau, P. J. Richards, B. Kerr, C. Hughes, B. Caterson, A. S. Williams, U. Junker, S. A. Jones, T. Clausen, and M. Ehrmann The Role of Human HtrA1 in Arthritic Disease J. Biol. Chem., March 10, 2006; 281(10): 6124 - 6129. [Abstract] [Full Text] [PDF]

				K. K. Zorn, T. Bonome, L. Gangi, G. V.R. Chandramouli, C. S. Awtrey, G. J. Gardner, J. C. Barrett, J. Boyd, and M. J. Birrer Gene Expression Profiles of Serous, Endometrioid, and Clear Cell Subtypes of Ovarian and Endometrial Cancer Clin. Cancer Res., September 15, 2005; 11(18): 6422 - 6430. [Abstract] [Full Text] [PDF]

				A. D. Santin, S. Cane, S. Bellone, M. Palmieri, E. R. Siegel, M. Thomas, J. J. Roman, A. Burnett, M. J. Cannon, and S. Pecorelli Treatment of Chemotherapy-Resistant Human Ovarian Cancer Xenografts in C.B-17/SCID Mice by Intraperitoneal Administration of Clostridium perfringens Enterotoxin Cancer Res., May 15, 2005; 65(10): 4334 - 4342. [Abstract] [Full Text] [PDF]

				M. J. Goodheart, J. M. Ritchie, S. L. Rose, J. P. Fruehauf, B. R. De Young, and R. E. Buller The Relationship of Molecular Markers of p53 Function and Angiogenesis to Prognosis of Stage I Epithelial Ovarian Cancer Clin. Cancer Res., May 15, 2005; 11(10): 3733 - 3742. [Abstract] [Full Text] [PDF]

				S. Grau, A. Baldi, R. Bussani, X. Tian, R. Stefanescu, M. Przybylski, P. Richards, S. A. Jones, V. Shridhar, T. Clausen, et al. Implications of the serine protease HtrA1 in amyloid precursor protein processing PNAS, April 26, 2005; 102(17): 6021 - 6026. [Abstract] [Full Text] [PDF]

				A. De Luca, M. De Falco, L. De Luca, R. Penta, V. Shridhar, F. Baldi, M. Campioni, M. G. Paggi, and A. Baldi Pattern of Expression of HtrA1 During Mouse Development J. Histochem. Cytochem., December 1, 2004; 52(12): 1609 - 1617. [Abstract] [Full Text] [PDF]

				A. De Luca, M. De Falco, V. Fedele, L. Cobellis, A. Mastrogiacomo, V. Laforgia, I. L. Tuduce, M. Campioni, D. Giraldi, M. G. Paggi, et al. The Serine Protease HtrA1 Is Upregulated in the Human Placenta During Pregnancy J. Histochem. Cytochem., July 1, 2004; 52(7): 885 - 892. [Abstract] [Full Text] [PDF]

				C. Oka, R. Tsujimoto, M. Kajikawa, K. Koshiba-Takeuchi, J. Ina, M. Yano, A. Tsuchiya, Y. Ueta, A. Soma, H. Kanda, et al. HtrA1 serine protease inhibits signaling mediated by Tgf{beta} family proteins Development, March 1, 2004; 131(5): 1041 - 1053. [Abstract] [Full Text] [PDF]

				J. M. Garcia Pedrero, M. P. Fernandez, R. O. Morgan, A. Herrero Zapatero, M. V. Gonzalez, C. Suarez Nieto, and J. P. Rodrigo Annexin A1 Down-Regulation in Head and Neck Cancer Is Associated with Epithelial Differentiation Status Am. J. Pathol., January 1, 2004; 164(1): 73 - 79. [Abstract] [Full Text] [PDF]

				A. De Luca, M. De Falco, A. Severino, M. Campioni, D. Santini, F. Baldi, M. G. Paggi, and A. Baldi Distribution of the Serine Protease HtrA1 in Normal Human Tissues J. Histochem. Cytochem., October 1, 2003; 51(10): 1279 - 1284. [Abstract] [Full Text] [PDF]

				J. Lai, J. Chien, J. Staub, R. Avula, E. L. Greene, T. A. Matthews, D. I. Smith, S. H. Kaufmann, L. R. Roberts**, and V. Shridhar** Loss of HSulf-1 Up-regulates Heparin-binding Growth Factor Signaling in Cancer J. Biol. Chem., June 13, 2003; 278(25): 23107 - 23117. [Abstract] [Full Text] [PDF]

				P. F. Macgregor and J. A. Squire Application of Microarrays to the Analysis of Gene Expression in Cancer Clin. Chem., August 1, 2002; 48(8): 1170 - 1177. [Abstract] [Full Text] [PDF]