This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Lassus, H. Articles by Butzow, R. Search for Related Content PubMed PubMed Citation Articles by Lassus, H. Articles by Butzow, R.

(American Journal of Pathology. 2001;159:35-42.)
© 2001 American Society for Investigative Pathology

Short Communications

Allelic Analysis of Serous Ovarian Carcinoma Reveals Two Putative Tumor Suppressor Loci at 18q22-q23 Distal to SMAD4, SMAD2, and DCC

Heini Lassus^*, Reijo Salovaara, Lauri A. Aaltonen and Ralf Butzow^*

From the Department of Obstetrics and Gynecology,^*
Helsinki University Central Hospital; and the Departments of Pathology
and Medical Genetics,
University of Helsinki, Helsinki, Finland

The distal half of chromosome arm 18q is frequently lost in ovarian carcinoma. To define the putative tumor suppressor locus/loci more precisely we performed allelic analysis with 27 polymorphic microsatellite markers located at 18q12.3-q23 in 64 serous and 9 mucinous ovarian carcinomas. Fifty-nine percent of the serous carcinomas, but only one (11%) of mucinous carcinomas, showed allelic loss at one or more loci (P = 0.018). In serous carcinomas, deletions were found to be associated with tumor grade and poor survival. The highest frequency of losses was detected at the distal part, 18q22-q23. Two minimal common regions of loss (MCRL) were identified at this region: MCRL1 between D18S465 and D18S61 at 18q22 (3.9 cM) and MCRL2 between D18S462 and D18S70 at 18q23 (5.8 cM). At 18q21.1, proximal to the MCRLs, there are three candidate tumor suppressor genes: SMAD4 (DPC4), SMAD2, and DCC. Their protein expression was studied by immunohistochemistry in normal ovarian tissue and serous carcinomas. Lost or very weak expression of SMAD4, SMAD2 and DCC was found in 28, 28, and 30% of serous carcinomas, respectively. Comparison of allelic loss and protein expression status indicated that none of these genes alone could be the target for the frequent allelic loss at 18q21.1. Together, these genes may account for a substantial proportion of the events, but not all of them. Thus, we propose that the frequent allelic loss at 18q is because of the effect of multiple genes, and there is at least one as yet unidentified tumor suppressor gene at 18q residing distal to SMAD4, SMAD2, and DCC involved in serous ovarian carcinoma.

This article has been cited by other articles:

				C. SALEK, P. MINARIKOVA, L. BENESOVA, V. NOSEK, R. STRNAD, M. ZAVORAL, and M. MINARIK Mutation Status of K-ras, p53 and Allelic Losses at 9p and 18q Are Not Prognostic Markers in Patients with Pancreatic Cancer Anticancer Res, May 1, 2009; 29(5): 1803 - 1810. [Abstract] [Full Text] [PDF]

				A Bamias, Z Yu, P. Weinberger, S Markakis, D Kowalski, R. Camp, D. Rimm, M. Dimopoulos, and A Psyrri Automated quantitative analysis of DCC tumor suppressor protein in ovarian cancer tissue microarray shows association with {beta}-catenin levels and outcome in patients with epithelial ovarian cancer Ann. Onc., December 1, 2006; 17(12): 1797 - 1802. [Abstract] [Full Text] [PDF]

				H. Alazzouzi, P. Alhopuro, R. Salovaara, H. Sammalkorpi, H. Jarvinen, J.-P. Mecklin, A. Hemminki, S. Schwartz Jr., L. A. Aaltonen, and D. Arango SMAD4 as a Prognostic Marker in Colorectal Cancer Clin. Cancer Res., April 1, 2005; 11(7): 2606 - 2611. [Abstract] [Full Text] [PDF]

				S. D. Pack, O. M. Alper, K. Stromberg, M. Augustus, M. Ozdemirli, A. M. Miermont, G. Klus, M. Rusin, R. Slack, N. F. Hacker, et al. Simultaneous Suppression of Epidermal Growth Factor Receptor and c-erbB-2 Reverses Aneuploidy and Malignant Phenotype of a Human Ovarian Carcinoma Cell Line Cancer Res., February 1, 2004; 64(3): 789 - 794. [Abstract] [Full Text] [PDF]

				T.-L. Erkinheimo, H. Lassus, P. Finne, B. P. van Rees, A. Leminen, O. Ylikorkala, C. Haglund, R. Butzow, and A. Ristimaki Elevated Cyclooxygenase-2 Expression Is Associated with Altered Expression of p53 and SMAD4, Amplification of HER-2/neu, and Poor Outcome in Serous Ovarian Carcinoma Clin. Cancer Res., January 15, 2004; 10(2): 538 - 545. [Abstract] [Full Text] [PDF]

				T.-L. Erkinheimo, H. Lassus, A. Sivula, S. Sengupta, H. Furneaux, T. Hla, C. Haglund, R. Butzow, and A. Ristimaki Cytoplasmic HuR Expression Correlates with Poor Outcome and with Cyclooxygenase 2 Expression in Serous Ovarian Carcinoma Cancer Res., November 15, 2003; 63(22): 7591 - 7594. [Abstract] [Full Text] [PDF]

				F. Beuschlein, B. D. Looyenga, S. E. Bleasdale, C. Mutch, D. L. Bavers, A. F. Parlow, J. H. Nilson, and G. D. Hammer Activin Induces x-Zone Apoptosis That Inhibits Luteinizing Hormone-Dependent Adrenocortical Tumor Formation in Inhibin-Deficient Mice Mol. Cell. Biol., June 1, 2003; 23(11): 3951 - 3964. [Abstract] [Full Text] [PDF]

				V.-M. Wasenius, S. Hemmer, E. Kettunen, S. Knuutila, K. Franssila, and H. Joensuu Hepatocyte Growth Factor Receptor, Matrix Metalloproteinase-11, Tissue Inhibitor of Metalloproteinase-1, and Fibronectin Are Up-Regulated in Papillary Thyroid Carcinoma: A cDNA and Tissue Microarray Study Clin. Cancer Res., January 1, 2003; 9(1): 68 - 75. [Abstract] [Full Text] [PDF]