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ABSTRACT: Endometrial cancer sequencing

PROVIDER: PRJNA990462 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25113336_1.fastq.gz	Fastqsanger.gz
	SRR25113336_2.fastq.gz	Fastqsanger.gz
	SRR25113337_1.fastq.gz	Fastqsanger.gz
	SRR25113337_2.fastq.gz	Fastqsanger.gz
	SRR25113338_1.fastq.gz	Fastqsanger.gz

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Comparative DNA methylome analysis of endometrioid adenocarcinoma, uterine papillary serous carcinoma, and normal endometrium

Project description:Classically, there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I; and uterine papillary serous carcinoma (UPSC), or Type II. These two types of cancers exhibit distinct DNA methylation levels in promoters of many genes. In EAC, many tumor suppressor genes were silenced due to DNA hypermethylation at their promoter region. However, promoters of many of these genes remained unmethylated in UPSC. Here, we described complete DNA methylome maps of endometrioid adenocarcinoma, uterine papillary serous carcinoma, and normal endometrium, by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq). We took a complementary and orthogonal approach to identify DNA methylation changes unique to the two endometrial cancer subtypes in an unbiased fashion. We generated complete DNA methylome maps for endometrioid adenocarcinoma (EAC, three samples), uterine papillary serous carcinomas (UPSC, three samples), and normal endometrium (pooled samples) by integrating data from methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq).

2014-10-12 | E-GEOD-51565 | biostudies-arrayexpress

Next-generation sequencing reveals miRNA expression profiles of endometrial cancer cells

Project description:Abundantly expressed oncogenic miRNAs in endometrial cancer cells are identified by next-generation sequencing.

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Pten and Dicer1 loss in the mouse uterus causes poorly-differentiated endometrial adenocarcinoma

Project description:Endometrial cancer remains the most common gynecological malignancy in the United States. While the loss of the tumor suppressor, PTEN, is well studied in endometrial cancer, recent studies suggest that DICER1, the endoribonuclease responsible for miRNA genesis, also plays a significant role in endometrial adenocarcinoma. To examine the effects of DICER1 deletion on mRNA and miRNA expression in endometrial cancer, poly-A RNA sequencing (RNA-seq) and small RNA sequencing were performed. Our findings indicate a relationship between appropriate miRNA expression and molecular signaling pathways in the development of poorly-differentiated endometrial adenocarcinoma.

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Comparative cistromics reveals genomic crosstalk between FOXA1 and ERα in tamoxifen-associated endometrial carcinomas

Project description:Tamoxifen, which is used to treat breast cancer, increases the risks of endometrial cancer. In this study, we performed a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer. ERα was found at active enhancers in endometrial cancer cells as marked by the presence of RNA polymerase II and the histone marker H3K27Ac. Our results define conserved sites for genomic interplay between FOXA1 and ERα in breast cancer and tamoxifen-associated endometrial cancer.

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Identification of long non-coding RNA expression patterns useful for molecular-based classification of type I endometrial cancers

Project description:Endometrial cancer represents the most frequent gynecologic malignant disease. Although several genetic alterations have been associated with increased risk, to date diagnosis and prognosis still rely on morphological features of the tumor, such as histological type, grading and invasiveness. As molecular-based classification is desirable for optimal treatment and prognosis of these cancers, , we explored the potential of lncRNAs as molecular biomarkers. To this end, we first identified by RNA sequencing (RNA-Seq) a set of lncRNAs differentially expressed in cancer vs normal endometrial tissues, a result confirmed also by analysis of RNA-Seq data of normal and cancerous endometrium from The Cancer Genome Atlas (TCGA). A significant association of a subset of these differentially expressed lncRNAs with tumor grade was then determined in 405 TCGA endometrial cancer profiles. Integrating endometrial cancer-specific expression profiles of long and small non-coding RNAs a functional association network was then identified. These results described for the first time a functional ‘core’ network, comprising small and long RNAs, whose deregulation is associated with endometrial neoplastic transformation, representing a set of cancer biomarkers that can be monitored and targeted for diagnosis, follow-up and therapy of these tumors.

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Project description:The identification of target genes at genome-wide association study (GWAS) loci is a major obstacle for GWAS follow-up. To identify candidate target genes at the 16 known endometrial cancer GWAS risk loci, we performed HiChIP chromatin looping analysis of endometrial cell lines. To enrich for enhancer-promoter interactions, a mechanism through which GWAS variation may target genes, we captured loops associated with H3K27Ac histone, characteristic of promoters and enhancers. Analysis of HiChIP loops contacting promoters revealed enrichment for endometrial cancer GWAS heritability and intersection with endometrial cancer risk variation identified 103 HiChIP target genes at 13 risk loci. Expression of four HiChIP target genes (SNX11, SRP14, HOXB2 and BCL11A) was associated with risk variation, providing further evidence for their regulation. Network analysis functionally prioritized a set of proteins that interact with those encoded by HiChIP target genes, and this set was enriched for pan-cancer and endometrial cancer drivers. Lastly, HiChIP target genes and prioritized interacting proteins were over-represented in pathways related to endometrial cancer development. In summary, we have generated the first global chromatin looping data from endometrial cells, enabling analysis of all known endometrial cancer risk loci and identifying biologically relevant candidate target genes.

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Universal Endometrial Cancer DNA Sequencing for Detection of Lynch Syndrome and Personalized Care

Project description:This clinical trial studies universal screening for deoxyribonucleic acid (DNA) mismatch repair deficiency in patients with endometrial cancer, mutations in the genes responsible for Lynch syndrome (inherited forms of endometrial cancers) and other DNA changes that could help guide treatment strategies. Universal tumor DNA sequencing may help doctors better understand how to personalize care, increase length of life, and increase quality of life in patients with endometrial cancer and their relatives.

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Gene expression analysis of murine endometrial cancer cell lines and murine normal endometrium

Project description:Endometrium-specific Cre-Lox deletion of both Pten and Tp53 via regulation of the progesterone receptor promoter is known to generate a spontaneous carcinogenic mouse model of endometrial cancer. A mouse endometrial cancer cell line, mECC, was established from the uterine carcinoma tumor tissue of its pure strain model generated by backcrossing in C57BL/6 mice. A high-grade endometrial cancer cell line (Highly Progressive mECC: HPmECC) was established by further introducing c-Myc in mECCs. RNA sequencing analysis was performed using cultured HPmECCs and mECCs, as well as primary cultured C57BL/6 normal endometrial cells for assessing the genetic characteristics of HPmECCs.

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