Expression signatures of TP53 mutations in serous ovarian cancers.
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2010-05-26
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BACKGROUND: Mutations in the TP53 gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease. METHODS: The TP53 coding region was sequenced in 89 frozen serous ovarian cancers, 40 early stage (I/II) and 49 advanced stage (III/IV). Affymetrix U133A expression data was used to define gene expression patterns by mutation, type of mutation, and cancer stage. RESULTS: Missense or chain terminating (null) mutations in TP53 were found in 59/89 (66%) ovarian cancers. Early stage cancers had a significantly higher rate of null mutations than late stage disease (38% vs. 8%, p < 0.03). In advanced stage cases, mutations were more prevalent in short term survivors than long term survivors (81% vs. 30%, p = 0.0004). Gene expression patterns had a robust ability to predict TP53 status within training data. By using early versus late stage disease for out of sample predictions, the signature derived from early stage cancers could accurately (86%) predict mutation status of late stage cancers. CONCLUSIONS: This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.
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Bernardini, Marcus Q, Tsukasa Baba, Paula S Lee, Jason C Barnett, Gregory P Sfakianos, Angeles Alvarez Secord, Susan K Murphy, Edwin Iversen, et al. (2010). Expression signatures of TP53 mutations in serous ovarian cancers. BMC Cancer, 10. p. 237. 10.1186/1471-2407-10-237 Retrieved from https://hdl.handle.net/10161/4356.
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Angeles Alvarez Secord
My primary research interest has focused on on novel therapeutics, biomarkers and clinical trial development for ovarian and endometrial cancer. My fundamental goal is to develop a strong translational research program at Duke University in the Gynecologic Oncology Division, where knowledge we glean from our basic science research can be incorporated into our clinical trial program. Specifically, my focus is on biologic therapy and molecular biomarkers to direct therapy in patients with ovarian and endometrial cancers to determine if a strategy that incorporates both clinical and genomic information can improve clinical outcome, minimize unnecessary toxicity, and impact positively on quality of life.
In addition I am interested in robotic-assisted laparoscopic surgery for women with endometrial, ovarian and cervical cancers, as well as for benign gynecologic conditions.
Susan Kay Murphy
Dr. Murphy is a tenured Associate Professor in the Department of Obstetrics and Gynecology and serves as Chief of the Division of Reproductive Sciences. As a molecular biologist with training in human epigenetics, her research interests are largely centered around the role of epigenetic modifications in health and disease.
Dr. Murphy has ongoing projects on gynecologic malignancies, including approaches to eradicate ovarian cancer cells that survive chemotherapy and later give rise to recurrent disease. Dr. Murphy is actively involved in many collaborative projects relating to the Developmental Origins of Health and Disease (DOHaD).
Her lab is currently working on preconception environmental exposures in males, particularly on the impact of cannabis on the sperm epigenome and the potential heritability of these effects. They are also studying the epigenetic and health effects of in utero exposures, with primary focus on children from the Newborn Epigenetics STudy (NEST), a pregnancy cohort she co-founded who were recruited from central North Carolina between 2005 and 2011. Dr. Murphy and her colleagues continue to follow NEST children to determine relationships between prenatal exposures and later health outcomes.
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