Project description:In the current study we performed characterization of 18 different in vitro models of high-grade serous (HGSOC), low-grade serous (LGSOC), mucinous (MOC), endometrioid (ENOC) and clear cell (CCOC) carcinoma. This study seeks to fill in this gap by generating an integrative Ovarian Cancer Regulatory Atlas (OCRA) of 18 ovarian normal and cancer cells profiled for epigenomic, transcriptomic, chromatin state and chromatin looping signatures.
Project description:The goal of the study was to examine the transcriptional profile of ovarian cancer cancers in order to develop validated clinically useful prognostic signatures with the potential to guide therapy decisions. Fresh frozen samples were prospectively collected from a series of 107 consecutive women with high-grade serous ovarian, primary peritonial, or fallopian tube cancer as well as high grade clear cell and endometrioid cancer who underwent surgery by a gynecologic oncologist at Mayo Clinic between 1994 and 2005. All patients received postoperative chemotherapy with a platinum agent, and 75% received a taxane. All patients signed an Institutional Review Board approved consent for bio-banking, clinical data extraction and molecular analysis. Median follow-up time was 35 months (range, 1-202 months). Fourteen patients (8%) were included in the TCGA study.
Project description:We have performed in-depth examination of single tissue sections from a collection of FFPE and Frozen treated tumors, as well as cell line material all originating from different subtypes of epithelial ovarian cancer (high-grade serous, clear cell, endometrioid). Data were prepared using a tandem mass tag 10plex protocol with MS3 analysis on an Orbitrap Fusion.
Project description:In the current study we performed epigenomic characterization of 13 different in vitro models of high-grade serous (HGSOC), low-grade serous (LGSOC), mucinous (MOC), endometrioid (ENOC) and clear cell (CCOC) carcinoma using ChIP-Seq for histone modication H3K4me1.
Project description:Background: Ovarian carcinomas consist of at least five distinct diseases: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker and molecular characterization may represent a more biologically relevant basis for grouping and treating this family of tumors, rather than site of origin. Molecular characteristics have become the new standard for clinical pathology, however development of tailored type-specific therapies is hampered by a failure of basic research to recognize that model systems used to study these diseases must also be stratified. Unrelated model systems do offer value for study of biochemical processes but specific cellular context needs to be applied to assess relevant therapeutic strategies. Methods: We have focused on the identification of clear cell carcinoma cell line models. A panel of 32 “ovarian cancer” cell lines has been classified into histological types using a combination of mutation profiles, IHC mutation-surrogates, and a validated immunohistochemical model. All cell lines were identity verified using STR analysis. Results: Many described ovarian clear cell lines have characteristic mutations (including ARID1A and PIK3CA) and an overall molecular/immuno-profile typical of primary tumors. Mutations in TP53 were present in the majority of high-grade serous cell lines. Advanced genomic analysis of bona-fide clear cell carcinoma cell lines also support copy number changes in typical biomarkers such at MET and HNF1B and a lack of any recurrent expressed re-arrangements. Conclusions: As with primary ovarian tumors, mutation status of cancer genes like ARID1A and TP53 and a general immuno-profile serve well for establishing histological type of ovarian cancer cell We describe specific biomarkers and molecular features to re-classify generic “ovarian carcinoma” cell lines into type specific categories. Our data supports the use of prototype clear cell lines, such as TOV21G and JHOC-5, and questions the use of SKOV3 and A2780 as models of high-grade serous carcinoma.
Project description:Biologically and clinically meaningful tumor classification schemes have long been sought. Some malignant epithelial neoplasms, such as those in the thyroid and endometrium, exhibit more than one pattern of differentiation, each associated with distinctive clinical features and treatments. In other tissues, all carcinomas, regardless of morphological type, are treated as though they represent a single disease. To better understand the biological and clinical features seen in the four major histological types of ovarian carcinoma (OvCa), we analyzed gene expression in 113 ovarian epithelial tumors using oligonucleotide microarrays. Global views of the variation in gene expression were obtained using PCA. These analyses show that mucinous and clear cell OvCas can be readily distinguished from serous OvCas based on their gene expression profiles, regardless of tumor stage and grade. In contrast, endometrioid adenocarcinomas show significant overlap with other histological types. Although high-stage/grade tumors are generally separable from low-stage/grade tumors, clear cell OvCa has a molecular signature that distinguishes it from other poor-prognosis OvCas. Indeed, 73 genes, expressed 2- to 29-fold higher in clear cell OvCas compared with each of the other OvCa types, were identified. Collectively, the data indicate that gene expression patterns in ovarian adenocarcinomas reflect both morphological features and biological behavior. Moreover, these studies provide a foundation for the development of new type-specific diagnostic strategies and treatments for ovarian cancer. cho-00156 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Material Types: synthetic_RNA, organism_part, whole_organism, total_RNA Disease States: Ovary cancer
Project description:The goal of the study was to further delineate the molecular signatures associated with high-grade serous ovarian cancer in order to develop validated clinically useful prognostic signatures with the potential to guide therapy decisions. Fresh frozen samples were prospectively collected from a series of 174 consecutive women with high-grade serous ovarian, primary peritonial, or fallopian tube cancer who underwent surgery by a gynecologic oncologist at Mayo Clinic betweern 1994 and 2005. All patients received postoperative chemotherapy with a platinum agent, and 75% received a taxane. All patients signed an Institutional Review Board approved consent for bio-banking, clinical data extraction and molecular analysis. Median follow-up time was 35 months (range, 1-202 months). Fourteen patients (8%) were included in the TCGA study.
Project description:99 individual ovarian tumors (37 endometrioid, 41 serous, 13 mucinous, and 8 clear cell carcinomas) and 4 individual normal ovary samples, each assayed on an Affymetrix HG_U133A array Experiment Overall Design: 99 individual ovarian tumors (37 endometrioid, 41 serous, 13 mucinous, and 8 clear cell carcinomas) and 4 individual normal ovary samples. RNA expression was analyzed using one Affymetrix HG_U133A array per sample.
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.