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Molecular Biology and Genetics |
Laboratory of Gynecological Oncology, Harvard Medical School, Brigham and Womens Hospital, Boston, Massachusetts 02115 [B. H. O., C. C., S. C. M.]; University of Pennsylvania Medical Center, Department of Obstetrics and Gynecology, Philadelphia, Pennsylvania 19103 [M. A.]; Division of Gynecological Oncology, Brigham and Womens Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 [M. G. M., R. S. B.]; Departments of Pathology [M. D., E. G. S.] and Gynecology Oncology [D. M. G.], The University of Texas M D Anderson Cancer Center, Houston, Texas 77030
The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous ovarian carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two tumors, we performed mutational analysis on tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous carcinomas was microdissected and retrieved using a PixCell laser-capture microscope. Stroma was dissected as an internal control. The DNA was extracted with proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary tumor compared with the primary tumor. For three patients, p53 mutations were identified in the BOTs that were absent from the carcinomas, suggesting a nonclonal origin for the carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous epithelial ovarian carcinoma.
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I.-M. Shih and R. J. Kurman Molecular Pathogenesis of Ovarian Borderline Tumors: New Insights and Old Challenges Clin. Cancer Res., October 15, 2005; 11(20): 7273 - 7279. [Abstract] [Full Text] [PDF] |
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I.-M. Shih and R. J. Kurman Ovarian Tumorigenesis: A Proposed Model Based on Morphological and Molecular Genetic Analysis Am. J. Pathol., May 1, 2004; 164(5): 1511 - 1518. [Abstract] [Full Text] [PDF] |
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