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Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma

ABSTRACT: Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma

PROVIDER: PRJNA1062692 | ENA |

REPOSITORIES: ENA

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Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma

Project description:The distal region of the uterine (Fallopian) tube is commonly associated with high-grade serous carcinoma (HGSC), the predominant and most aggressive form of ovarian or extra-uterine cancer. Specific cell states and lineage dynamics of the adult tubal epithelium (TE) remain insufficiently understood, hindering efforts to determine the cell of origin for HGSC. Here, we report a comprehensive census of cell types and states of the mouse uterine tube. We show that distal TE cells expressing the stem/progenitor cell marker Slc1a3 can differentiate into both secretory (Ovgp1+) and ciliated (Fam183b+) cells. Inactivation of Trp53 and Rb1, whose pathways are commonly altered in HGSC, leads to elimination of targeted Slc1a3+ cells by apoptosis, thereby preventing their malignant transformation. In contrast, pre-ciliated cells (Krt5+, Prom1+, Trp73+) remain cancer-prone and give rise to serous tubal intraepithelial carcinomas and overt HGSC. These findings identify transitional pre-ciliated cells as a previously unrecognized cancer-prone cell state and point to pre-ciliation mechanisms as novel diagnostic and therapeutic targets.

2024-09-18 | GSE252786 | GEO

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [CNV]

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.

2017-08-01 | GSE102085 | GEO

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [miRNA expression]

2017-07-28 | GSE101976 | GEO

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [RNA-Seq]

2017-08-01 | GSE102073 | GEO

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma

Project description:Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma

| PRJNA396576 | ENA

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [RNA-Seq; normal samples]

2018-05-15 | GSE114493 | GEO

The methylomic landscape of fallopian tube lesions associated with ovarian high grade serous carcinoma

Project description:The current paradigm in the development of high-grade serous carcinomas (HGSCs) proposes that the majority of HGSCs arise from precursor serous tubal intraepithelial carcinoma (STIC) lesions of the fallopian tube. The goal of this study is to identify genomic regions that exhibit high-specificity differential hypermethylation for potential use as biomarkers for detecting STIC and HGSC at stages when curative intervention likely remains feasible.

2020-07-29 | GSE155311 | GEO

Transcription profiling of human non-malignant fallopian tube epithelium and high grade serous carcinoma.

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.

2008-06-18 | E-GEOD-10971 | biostudies-arrayexpress

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [RNA-Seq normal samples]

Project description:Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [RNA-Seq normal samples]

| PRJNA471533 | ENA

LncRNA and mRNA expression profiles in High-grade serous ovarian cancer, Low-grade serous ovarian cancer and Normal fallopian tube

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.

2020-02-12 | GSE135886 | GEO

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