Journal
GYNECOLOGIC ONCOLOGY
Volume 130, Issue 3, Pages 565-569Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2013.06.016
Keywords
Ovarian cancer; p53 mutation; Wild-type p53; EDA2R; Survival statistics; Collagen VI
Categories
Funding
- National Institutes of Health
- University of Texas MD Anderson Cancer Center Specialized Program of Research Excellence in Ovarian Cancer [P50 CA08369]
- MD Anderson's Cancer Center Support Grant [CA016672]
- Blanton-Davis Ovarian Cancer Research Program
- Sara Brown Musselman Fund for Serous Ovarian Cancer Research
- National Cancer Institute-Department of Health and Human Services-National Institutes of Health Training of Academic Oncologists Grant [T32 CA101642]
- [CA133057]
- NATIONAL CANCER INSTITUTE [R01CA133057, P30CA016672, P50CA083639] Funding Source: NIH RePORTER
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Objective. The objective of this study is to investigate whether wild-type TP53 status in high-grade serous ovarian carcinoma is associated with poorer survival. Methods. Clinical and genomic data of 316 sequenced samples from The Cancer Genome Atlas (TCGA) ovarian high-grade serous carcinoma study were downloaded from TCGA data portal. Association between wild-type TP53 and survival was analyzed with Kaplan Meier method and Cox regression. The diagnosis of high-grade serous carcinomas was evaluated by reviewing pathological reports and high-resolution hematoxylin and eosin (H&E) images from frozen sections. The authenticity of wild-type TP53 in these tumor samples was assessed by analyzing SNP array data with ASCAT algorithm, reverse phase protein array (RPPA) data and RNAseq data. Results. Fifteen patients with high grade serous ovarian carcinomas were identified to have wild-type TP53, which had significantly shorter survival and higher chemoresistance than those with mutated TP53. The authenticity of wild-type TP53 status in these fifteen patients was supported by SNP array, RPPA, and RNAseq data. Except four cases with mixed histology, the classification as high grade serous carcinomas was supported by pathological reports and H&E images. Using RNAseq data, it was found that EDA2R gene, a direct target of wild-type TP53, was highly up-regulated in samples with wild-type TP53 in comparison to samples with either nonsense or missense TP53 mutations. Conclusion. Although patients with wild-type TP53 ovarian cancer were rare in the TCGA high grade ovarian serous carcinomas cohort, these patients appeared to have a poorer survival and were more chemoresistant than those with mutated TP53. Differentially expressed genes in these TP53 wild-type tumors may provide insight in the molecular mechanism in chemotherapy resistance. (C) 2013 Elsevier Inc. All rights reserved.
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