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Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes [RNA-Seq]

ABSTRACT: Epithelial ovarian cancer, or ovarian carcinoma (OC), is a diverse disease. Two of the rarer subtypes, clear cell OC (CCOC) and endometrioid OC (ENOC), both arise from ovarian endometriotic cysts, particularly atypical endometriosis. CCOC and ENOC have similar mutation profiles and share a common cell of origin, but their cellular phenotypes and clinical outcomes are distinct; in particular, CCOC has poor clinical survival. The most well-known difference between the histotypes is the universal overexpression of HNF1B (Hepatocyte nuclear factor-1β) in clear cell tumors and overexpression of ESR1 in ENOC. It is not well understood how these discrete histotypes arise from the same cell of origin. Via transcriptional (n=57) and DNA methylation analysis (N=127) of these rare tumors, we show that CCOC closely resembles secretory endometrium in transcriptional profile; whereas ENOC transcriptomes resemble proliferative endometrium.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226870 | GEO | 2023/10/13

REPOSITORIES: GEO

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Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes [methylation]

Project description:Epithelial ovarian cancer, or ovarian carcinoma (OC), is a diverse disease. Two of the rarer subtypes, clear cell OC (CCOC) and endometrioid OC (ENOC), both arise from ovarian endometriotic cysts, particularly atypical endometriosis. CCOC and ENOC have similar mutation profiles and share a common cell of origin, but their cellular phenotypes and clinical outcomes are distinct; in particular, CCOC has poor clinical survival. The most well-known difference between the histotypes is the universal overexpression of HNF1B (Hepatocyte nuclear factor-1β) in clear cell tumors and overexpression of ESR1 in ENOC. It is not well understood how these discrete histotypes arise from the same cell of origin. Via transcriptional (n=57) and DNA methylation analysis (N=127) of these rare tumors, we show that CCOC closely resembles secretory endometrium in transcriptional profile; whereas ENOC transcriptomes resemble proliferative endometrium.

2023-10-13 | GSE226823 | GEO

Exploring the tumor micro-environment of ovarian cancer histotypes and tumor sites

Project description:Ovarian cancer is a common, malignant cancer in the female reproductive system. Despite the commonly affected tissue ovary, ovarian cancer is a heterogeneous disease consisting of at least five different histological subtypes and varying clinical features, cells of origin, molecular composition, risk factors, and treatments. With cumulative studies on the tumor microenvironment, a comprehensive landscape of the constituent cell types, and their interactions are yet to be established in ovarian cancer and its histotypes. Further characterization of tumor progression, metastasis, and various histotypes is needed to connect molecular signatures to pathological grading for tailored diagnosis and treatment. In this study, we leveraged high-resolution single-cell RNA sequencing technology to elucidate the cellular compositions on 21 solid tumor samples collected from 12 patients with six ovarian cancer histotypes and both primary (ovaries) and metastatic (omentum, rectum) sites. The diverse collection allows us to zoom in on histotype and tumor site-specific expression patterns of cells in the tumor and identify key marker genes and ligand-receptor pairs that are active in the ovarian tumor microenvironment. Our findings can be used in improving disease stratification and design of customized treatment.

2023-12-15 | GSE235931 | GEO

A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes

Project description:Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Using data from large endometriosis and EOC genome-wide association meta-analyses we estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and EOC histotypes, and identify shared susceptibility loci. We estimate a significant genetic correlation (rg) between endometriosis and clear cell (rg=0.71), endometrioid (rg=0.48) and high-grade serous (rg=0.19) ovarian cancer, associations supported by Mendelian randomization analyses. Bivariate meta-analysis identify 28 loci associated with both endometriosis and EOC, including 19 with evidence for a shared underlying association signal. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlights several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases.

2022-03-07 | GSE197928 | GEO

The histotype-specific copy-number landscape of ovarian cancer (expression Japan)

Project description:Ovarian cancer is characterized by multiple structural aberrations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and till date, the histotype-specific copy number landscape has been difficult to elucidate. To dissect the heterogeneity of ovarian cancer and understand the pathogenesis of its various histotypes, we developed an in silico hypothesis-driven workflow to identify histotype-specific copy number aberrations across multiple datasets of epithelial ovarian cancer. In concordance with previous studies on global copy number changes, our study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here a comprehensive histotype-specific copy number landscape of ovarian cancer and showed that there is genomic diversity between the histotypes; some involving well known cancer genes and some novel potential driver genes. Besides preferential occurrence of alterations in some histotypes, opposite trends of alteration were observed; such as ERBB2 amplification in mucinous but deletion in serous tumors. The landscape highlights the need for identifying histotype-specific aberrations in ovarian cancer and present potential to tailor management of ovarian cancer based on molecular signature of histotypes. 56 samples containing the 4 histotypes were used for this study. It contained 12 clear cell carcinoma, 6 endometrioid adenocarcinoma, 2 mucinous adenocarcinoma, 5 mucinous-borderline tumors, 26 serous adenocarcinoma, and 5 serous-borderline tumors.

2012-10-25 | E-GEOD-30274 | biostudies-arrayexpress

The histotype-specific copy-number landscape of ovarian cancer (copy number Japan)

2012-10-25 | E-GEOD-30283 | biostudies-arrayexpress

The histotype-specific copy-number landscape of ovarian cancer (expression Taiwan)

Project description:Ovarian cancer is characterized by multiple structural aberrations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and till date, the histotype-specific copy number landscape has been difficult to elucidate. To dissect the heterogeneity of ovarian cancer and understand the pathogenesis of its various histotypes, we developed an in silico hypothesis-driven workflow to identify histotype-specific copy number aberrations across multiple datasets of epithelial ovarian cancer. In concordance with previous studies on global copy number changes, our study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here a comprehensive histotype-specific copy number landscape of ovarian cancer and showed that there is genomic diversity between the histotypes; some involving well known cancer genes and some novel potential driver genes. Besides preferential occurrence of alterations in some histotypes, opposite trends of alteration were observed; such as ERBB2 amplification in mucinous but deletion in serous tumors. The landscape highlights the need for identifying histotype-specific aberrations in ovarian cancer and present potential to tailor management of ovarian cancer based on molecular signature of histotypes. 42 archived frozen tumor samples collected from Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taiwan, containing 8 clear cell, 3 mucinous, and 31 serous.

2012-10-25 | E-GEOD-30284 | biostudies-arrayexpress

Identification of Novel Therapeutic Targets in Microdissected Clear Cell Ovarian Cancers

Project description:To identify the gene signature accounting for the distinct clinical outcomes in ovarian clear cell cancer patients Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this, patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. Arrays analyzed using BRB ArrayTools and PathwayStudio software was used to identify the signaling pathways. Gene expression profiling was completed for 10 clear cell ovarian cancer specimens and 10 normal ovarian surface epithelium using the Affymetrix human U133 Plus 2.0 Arrays

2011-05-24 | E-GEOD-29450 | biostudies-arrayexpress

Identification of Novel Therapeutic Targets in Microdissected Clear Cell Ovarian Cancers

2011-05-24 | GSE29450 | GEO

The histotype-specific copy-number landscape of ovarian cancer (copy number SNP)

Project description:Ovarian cancer is characterized by multiple structural aberrations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and till date, the histotype-specific copy number landscape has been difficult to elucidate. To dissect the heterogeneity of ovarian cancer and understand the pathogenesis of its various histotypes, we developed an in silico hypothesis-driven workflow to identify histotype-specific copy number aberrations across multiple datasets of epithelial ovarian cancer. In concordance with previous studies on global copy number changes, our study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here a comprehensive histotype-specific copy number landscape of ovarian cancer and showed that there is genomic diversity between the histotypes; some involving well known cancer genes and some novel potential driver genes. Besides preferential occurrence of alterations in some histotypes, opposite trends of alteration were observed; such as ERBB2 amplification in mucinous but deletion in serous tumors. The landscape highlights the need for identifying histotype-specific aberrations in ovarian cancer and present potential to tailor management of ovarian cancer based on molecular signature of histotypes. 46 archived frozen tumor samples collected from Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taiwan, containing 9 clear cell, 6 mucinous, and 31 serous. Data was pre-processed and normalized with Hapmap CHB using the Affymetric Genotyping Console.

2012-10-25 | E-GEOD-30300 | biostudies-arrayexpress

Comprehensive RNA sequencing of healthy human endometrium at two time points of the menstrual cycle

Project description:mRNA, sncRNA and lncRNA show a clear difference in expression between proliferative phase and 7–9 days after ovulation, thorough described together with lncRNA, snoRNA and snRNA not previously reported in healthy human endometrium

2016-12-01 | GSE86491 | GEO

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