Project description:Fallopian tube epithelium is the tissue-of-origin of most high grade serous papillary ovarian carcinoma. This tumor has been exensively investigated and sequenced but expression profiling data of normal fallopian tube epithelial cells is still rare. This project compares the miRNA profiles of high grade serous papillary ovarian tumors (FFPE and fresh frozen) to that of normal unmatched epithelial cells from resected fallopian tubes.
Project description:The purpose of this study was to identify molecular alterations potentially involved in predisposition to adnexal serous carcinoma (SerCa) in the non-malignant fallopian tube epithelium (FTE) of BRCA1/2-mutation carriers, given recent evidence implicating the distal FTE as a common source for SerCa. Experiment Overall Design: We obtained and compared gene expression profiles of laser capture microdissected non-malignant distal FTE from 12 known BRCA1/2-mutation carriers (FTEb) and 12 control women (FTEn) during the luteal and follicular phase, as well as 13 high grade tubal and ovarian SerCa.
Project description:In this study, we performed miRNA profiles analysis of high-grade serous ovarian carcinoma compared to normal fallopian tube fimbria using microarray (Exiqon, Denmark) to evaluate their potential role in the pathogenesis of uterine leiomyoma. miRNA profiling analysis of the 10 samples including 5 high-grade serous ovarian carcinomas and 5 normal fallopian tube fimbria.
Project description:Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histologic analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal appearing p53-positive epithelium that are similar to “p53 signatures” in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these noninvasive precursor lesions, we also identified invasive adenocarcinoma in the ovary of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and WT C57BL/6. One of these genes, Top2a, which encodes topoisomerase II-alpha, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and specifically elevated in mouse STICs, but not in surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade, and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumorigenesis, as well as for developing novel approaches for the prevention, diagnosis, and therapy of this disease. Keywords: transgenic mouse model, ovarian cancer, fallopian tube, intraepithelial carcinoma 6 mouse fallopian tubes (FT) were analyzed with experimental repeats; 3 wildtype C57BL6 mice (FT) and 3 transgenic mogp-TAg (FT), with one set of each at 7, 8 and 9 weeks of age.
Project description:High-grade serous ovarian, fallopian tube or peritoneal carcinoma is an aggressive subtype that frequently develops resistance to chemotherapy. It remains controversial whether the resistance is caused by the acquisition of new molecular aberrations or alternatively through the selection of rare preexisting tumor clones. To address this question, we applied single cell RNA sequencing to depict the tumor landscape of a single case of advanced high-grade serous fallopian tube carcinoma during neoadjuvant chemotherapy (NACT).
Project description:The purpose of this study was to identify molecular alterations potentially involved in predisposition to adnexal serous carcinoma (SerCa) in the non-malignant fallopian tube epithelium (FTE) of BRCA1/2-mutation carriers, given recent evidence implicating the distal FTE as a common source for SerCa. Keywords: disease state analysis
Project description:Ovarian cancer is the most lethal gynecologic cancer. High-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype, accounting for three quarters of ovarian cancer. To clarify the changes of gene expression in serous ovarian cancer, we performed lncRNA and mRNA microarrays to identify differentially expressed lncRNAs and mRNAs in High-grade and Low-grade serous ovarian carcinoma compared with Normal fallopian tube.
Project description:Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histologic analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal appearing p53-positive epithelium that are similar to “p53 signatures” in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these noninvasive precursor lesions, we also identified invasive adenocarcinoma in the ovary of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and WT C57BL/6. One of these genes, Top2a, which encodes topoisomerase II-alpha, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and specifically elevated in mouse STICs, but not in surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade, and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumorigenesis, as well as for developing novel approaches for the prevention, diagnosis, and therapy of this disease. Keywords: transgenic mouse model, ovarian cancer, fallopian tube, intraepithelial carcinoma
Project description:Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intraepithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. RNA sequence and miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.
Project description:Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intraepithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. RNA sequence and miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.