Abstract
Serous ovarian carcinomas are the predominant epithelial ovarian cancer subtype and it has been widely believed that some or all of these may arise from precursors derived from the ovarian surface epithelium or fimbriae, although direct molecular evidence for this is limited. This study aimed to conduct copy number (CN) analysis using a series of benign and borderline serous ovarian tumors to identify underlying genomic changes that may be indicative of early events in tumorigenesis. High resolution CN analysis was conducted on DNA from the epithelial and fibroblast components of a cohort of benign (N = 39) and borderline (N = 24) serous tumors using the Affymetrix OncoScan assay and SNP6.0 arrays. CN aberrations were detected in the epithelium of only 2.9% (1 of 35) of serous cystadenomas and cystadenofibromas. In contrast, CN aberrations were detected in the epithelium of 67% (16 of 24) of the serous borderline tumors (SBT). Unexpectedly, CN aberrations were detected in the fibroblasts of 33% (13 of 39) of the benign serous tumors and in 15% (3 of 20) of the SBTs. Of the 16 cases with CN aberrations in the fibroblasts, 12 of these carried a gain of chromosome 12. Chromosome 12 trisomy has been previously identified in pure fibromas, supporting the concept that a significant proportion of benign serous tumors are in fact primary fibromas with an associated cystic mass. This is the first high resolution genomic analysis of benign serous ovarian tumors and has shown not only that the majority of benign serous tumors have no genetic evidence of epithelial neoplasia but that a significant proportion may be more accurately classified as primary fibromas.
Highlights
A total of 14 serous cystadenomas and 21 serous cystadenofibromas were identified where copy number (CN) could be analyzed in matching epithelium, fibroblasts, and germ line DNA
All tissues were microdisssected to achieve more than 80% pure epithelial or fibroblast cell populations (Supplementary Fig. S2), which we have shown previously is sufficient purity to reliably identify CN aberrations and LOH [29]
This study has shown that CN/LOH aberrations in the epithelium of benign serous tumors are rare, occurring in just one (2.9%) of cases studied, whereas aberrations in the fibromatous components were more frequent, occurring in 33.3% of cases
Summary
Authors' Affiliations: 1Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, Melbourne; 2Department of Pathology, University of Melbourne, Parkville, Victoria; 3Anatomical Pathology, University of Sydney and University of Western Sydney at Westmead Hospital; 4Department of Gynaecological Oncology, 5Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia; 6The Department of Pathology and Laboratory Medicine, University of British Columbia; 7Genetic Pathology Evaluation Centre of the Prostate Research Centre and Department of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada; 8Department of Pathology, Stanford University School of Medicine, Stanford, California. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/). K.L. Gorringe and I.G. Campbell are co-senior authors.
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