Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas

• Published in: International journal of cancer Vol. 119; no. 6; pp. 1345 - 1353
• Main Authors: Tuhkanen, Hanna, Anttila, Maarit, Kosma, Veli‐Matti, Heinonen, Seppo, Juhola, Matti, Helisalmi, Seppo, Kataja, Vesa, Mannermaa, Arto
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.09.2006; Wiley-Liss
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - pathology; Chromosome Aberrations; Chromosomes, Human, Pair 18 - genetics; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - pathology; DCC Receptor; epithelial–mesenchymal transition (EMT); Female; Female genital diseases; Gene Dosage; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Middle Aged; multiplex ligation‐dependent probe amplification (MLPA); Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - pathology; oncogene; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Receptors, Cell Surface - genetics; Stromal Cells - pathology; tumor suppressor gene; Tumor Suppressor Proteins - genetics; Tumors; Human; Gene dosage; Genetic gain; Ovary carcinoma; Ovary cancer; Malignant tumor; Mesenchymal cell; Cell transformation; oncogene; Female genital diseases; Ovarian diseases; epithelial-mesenchymal transition (EMT); Cancerology; Multiplex ligation dependent probe amplification; C-Onc gene; Deletion; Genetics; multiplex ligation-dependent probe amplification (MLPA); Stromal cell; Protooncogene; Tumor suppressor gene
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21785

Stromal cells are an active and integral part of epithelial neoplasms. We have previously observed allelic imbalance on chromosome 3p21 in both stromal and epithelial cells of ovarian tumors. This study was designed to explore gene dosage alterations throughout human chromosomes from stromal and epithelial cells of epithelial ovarian carcinomas. Thirteen stromal and 24 epithelial samples, microdissected from epithelial ovarian carcinomas, were analyzed using multiplex ligation‐dependent probe amplification technique. Analysis covered 110 cancer related genes. Frequent genetic alterations were detected both in the stroma and epithelium of ovarian carcinomas. The mean number of altered genes per tumor was 10.8 in stroma and 23.6 in epithelium. In the stroma, the mean number of gains was 6.6 and of losses 4.2 and in the epithelium 13.7 and 9.9. The high number of changes associated with advanced tumor stage (p = 0.035) and death due to ovarian cancer (p = 0.032). The most frequent alteration was the deletion of the deleted in colorectal carcinoma (DCC) on chromosome 18q21.3 in 62% of samples. Loss of DCC was related to endometrioid subtype (p = 0.033). Large chromosomal aberrations were detected on the basis of alterations in adjacent genes. Most importantly, 38 genes showed similar genetic alterations (gain–gain or loss–loss) in stromal and epithelial compartments of 11 tumor pairs. Thus, frequent genetic alterations in stromal cells of epithelial ovarian carcinomas resembled those of malignant epithelial cells and may indicate a common precursor cell type. Epithelial–mesenchymal transition may generate transformed cancer cells and modify the tumor microenvironment with distinct properties. © 2006 Wiley‐Liss, Inc.