Project description:High-grade serous ovarian cancer is the most aggressive histological type of epithelial ovarian cancer, which is characterized by a high frequency of somatic TP53 mutations. To provide a better understanding of the molecular mechanisms involved in the pathogenesis of these cancers and to develop a risk classification system, we conducted profiling of the copy number alterations present in these tumors. Thirty patients who were diagnosed as high-grade serous ovarian cancer were recruited in this study. Affymetrix SNP array were performed according to the manufacturer's directions on DNA extracted from high-grade serous ovarian cancer tissues or peripheral blood samples. The Japanese Serous Ovarian Cancer Study Group
Project description:The JGOG3025 study was conducted by the Japanese Gynecologic Oncology Group (JGOG) on 710 patients with epithelial ovarian cancer (NCT03159572). In the JGOG3025-TR2 study, fresh frozen tumor tissues from 274 and 15 cases diagnosed as stage II or higher high-grade serous carcinoma (HGSC) or high-grade endometrioid carcinoma (HGEC) in the central pathological review were submitted to SNP array, total RNA-sequencing, and DNA methylation array analyses.
Project description:The JGOG3025 study was conducted by the Japanese Gynecologic Oncology Group (JGOG) on 710 patients with epithelial ovarian cancer (NCT03159572). In the JGOG3025-TR2 study, fresh frozen tumor tissues from 274 and 15 cases diagnosed as stage II or higher high-grade serous carcinoma (HGSC) or high-grade endometrioid carcinoma (HGEC) in the central pathological review were submitted to SNP array, total RNA-sequencing, and DNA methylation array analyses.
Project description:The JGOG3025 study was conducted by the Japanese Gynecologic Oncology Group (JGOG) on 710 patients with epithelial ovarian cancer (NCT03159572). In the JGOG3025-TR2 study, fresh frozen tumor tissues from 274 and 15 cases diagnosed as stage II or higher high-grade serous carcinoma (HGSC) or high-grade endometrioid carcinoma (HGEC) in the central pathological review were submitted to SNP array, total RNA-sequencing, and DNA methylation array analyses.
Project description:Low-grade serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors, yet the progression from serous borderline tumors to low-grade serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the two groups. Expression profiles were generated from 6 human ovarian surface epithelia (HOSE), 8 serous borderline ovarian tumors (SBOT), 13 low-grade serous ovarian carcinomas (LG), and 22 high-grade serous ovarian carcinomas (HG). The anterior gradient homolog 3 (AGR3) gene was found to be highly upregulated in serous borderline ovarian tumors; this finding was validated by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. Anti-AGR3 immunohistochemistry was performed on an additional 56 LG and 103 HG tissues and the results were correlated with clinical data. Expression profiling determined that 1254 genes were differentially expressed (P < 0.005) between SBOT, LG and HG tumors. Serous borderline ovarian tumors exhibited robust positive staining for AGR3, with a lower percentage of tumor cells stained in LG and HG. Immunofluorescence staining indicated that AGR3 expression was limited to ciliated cells. Tumor samples with a high percentage (>10%) of AGR3 positively stained tumor cells were associated with improved longer median survival in both the LG (P = 0.013) and HG (P = 0.008) serous ovarian carcinoma groups. The progression of serous borderline ovarian tumors to low-grade serous ovarian carcinoma may involve the de-differentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with low-grade and high-grade serous ovarian carcinomas. Total RNA were extracted from microdissected human ovarian surface epithelia (HOSE, n=6), and microdissected serous borderline ovarian tumors (LMP, n=8), low-grade serous ovarian carcinomas (LGOSC, n=13), and 22 high-grade serous ovarian carcinomas (HGOSC, n=22). Gene Expression profiles were then generated with commercial GeneChip Human Genome U133 Plus 2.0 Array. dChip was used to identify significant differentially expressed genes between LMP/LGOSC and HGOSC
Project description:To demonstrate the use of a whole-genome oligonucleotide array to perform expression profiling on a series of microdissected late-stage, high-grade papillary serous ovarian adenocarcinomas to establish a prognostic gene signature correlating with survival and to identify novel survival factors in ovarian cancer. Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. We identify and validate a prognostic gene expression signature correlating with survival in a series of microdissected serous ovarian tumors. Experiment Overall Design: We identified 53 advanced stage, high-grade primary tumor specimens and 10 normal ovarian surface epithelium (OSE) brushings.
Project description:Epithelial ovarian cancer is a very heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Rational therapeutic approaches need to account for interpatient and intratumoral heterogeneity in treatment design. Detailed characterization of in vitro models representing the different histological and molecular subtypes is therefore imperative. Strikingly, from ~100 available ovarian cancer cell lines the origin and which subtype they represent is largely unknown. We have extensively and uniformly characterized 39 ovarian cancer cell lines (with mRNA/microRNA expression, exon sequencing, dose response curves for clinically relevant therapeutics) and obtained all available information on the clinical features and tissue of origin of the original ovarian cancer to refine the putative histological subtypes. From 39 ovarian cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes (21 Epithelial, 7 Round, 12 Spindle) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes for the Spindle subtype. Clinical validation showed a clear association of the spindle-like tumors with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the morphological subtypes associated with the molecular C1-6 subtypes identified by Tothill et al. [1], Spindle clustered with C1-stromal subtype, Round with C5-mesenchymal and Epithelial with C4 subtype. We provide a uniformly generated data resource for 39 ovarian cancer cell lines, the ovarian cancer cell line panel (OCCP). This should be the basis for selecting models to develop subtype specific treatment approaches, which is very much needed to prolong the survival of ovarian cancer patients. Gene expression was measured for 32 ovarian cancer cell lines using the GeneChip Human Exon 1.0 ST Array (Affymetrix). Morphological subtypes were assigned based on cell morphology, size, growth pattern and proliferation rate during culturing of the cell lines.
Project description:Low-grade serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors, yet the progression from serous borderline tumors to low-grade serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the two groups. Expression profiles were generated from 6 human ovarian surface epithelia (HOSE), 8 serous borderline ovarian tumors (SBOT), 13 low-grade serous ovarian carcinomas (LG), and 22 high-grade serous ovarian carcinomas (HG). The anterior gradient homolog 3 (AGR3) gene was found to be highly upregulated in serous borderline ovarian tumors; this finding was validated by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. Anti-AGR3 immunohistochemistry was performed on an additional 56 LG and 103 HG tissues and the results were correlated with clinical data. Expression profiling determined that 1254 genes were differentially expressed (P < 0.005) between SBOT, LG and HG tumors. Serous borderline ovarian tumors exhibited robust positive staining for AGR3, with a lower percentage of tumor cells stained in LG and HG. Immunofluorescence staining indicated that AGR3 expression was limited to ciliated cells. Tumor samples with a high percentage (>10%) of AGR3 positively stained tumor cells were associated with improved longer median survival in both the LG (P = 0.013) and HG (P = 0.008) serous ovarian carcinoma groups. The progression of serous borderline ovarian tumors to low-grade serous ovarian carcinoma may involve the de-differentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with low-grade and high-grade serous ovarian carcinomas.