Somatic Mutational Analysis by Exome Sequencing Endometrial Carcinosarcomas
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ABSTRACT:
PROVIDER: PRJNA326037 | ENA |
REPOSITORIES: ENA
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Project description:Somatic Mutational Analysis by Exome Sequencing Late-Stage Endometrioid Endometrial Carcinoma
| PRJNA326146 | ENA
Project description:Somatic Mutational Analysis by Exome Sequencing Endometrial Carcinosarcomas
| PRJNA326038 | ENA
Project description:Primary uveal melanomas show multiple genetic alterations. To determine mutational status of six human primary uveal melanomas, we performed whole exome sequencing (WES) and called Single Nucleotide Polimorphism (SNPs) to identify somatic mutations in these human primary uveal melanomas.
2021-01-25 | GSE138664 | GEO
Project description:The molecular events implicated in the development of endometrial carcinosarcoma remain poorly understood. Using complementary DNA microarrays, we analyzed a group of 15 endometrial carcinosarcomas and compared their gene expression profiles with those obtained from a group of 23 endometrioid endometrial carcinomas. We demonstrated changes in the expression of genes modulating processes such as the epithelial to mesenchymal transition, muscle differentiation, the expression of cancer/testis antigens, and immune response in endometrial carcinosarcomas. The high mobility group AT-hook 2 gene is an embryonic nuclear factor that mediates epithelial to mesenchymal transition in various tumor models, and it was among the genes overexpressed in endometrial carcinosarcomas. High mobility group AT-hook 2 overexpression was confirmed in 54% of endometrial carcinosarcomas by quantitative real time-polymerase chain reaction and immunohistochemistry. Moreover, we found a significant inverse correlation between the expression of high mobility group AT-hook 2 and let-7b, a member of the let-7 family of microRNAs that represses high mobility group AT-hook 2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis that is implicated in cancer progression and metastasis. Finally, high mobility group AT-hook 2 overexpression, which was detected in less than 3% of endometrioid endometrial carcinomas, was observed in many nonendometrioid carcinomas (46% of 28 samples). This pattern of expression, restricted to nonendometrioid carcinomas and endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in endometrial carcinogenesis that is associated with aggressive phenotypes and points to its potential use as a marker to distinguish between endometrioid and nonendometrioid tumors.
2012-11-01 | GSE33723 | GEO
Project description:Biological implications of healthy- and tumor-specific ERα cistromes in endometrial tumors have largely been understudied. Moreover, the functional impact of non-coding somatic variants has commonly been underexplored and remained elusive. This study is aimed to provide functional interpretation of non-coding somatic variants associated with tumor-specific ERα cistrome. Integrating the ChIP-seq analyses with the whole genome sequencing from the set of metastatic endometrial tumors and matched controls we observed that tumor-specific ERα cistrome is enriched for somatic variants. Additionally, H3K27Ac Hi-ChIP in cancer cell lines identified potential target genes of tumor-specific enhancers and coincident variants. We aim to employ CRISPR to identify tumor-specific ERα enhancers and target genes critical for estrogen-driven proliferation of endometrial cancer-cell lines. Through multidimensional omics data integration, our study is specifically geared to shed new lights on the molecular mechanisms of endometrial cancer development and progression and the functional impact of non-coding somatic mutations.
2025-04-15 | PXD029822 | Pride
Project description:Full title: comparison of the genomic (arrayCGH) profiles of endometrial cancer with and without prior prolonged tamoxifen treatment for primary breast cancer Purpose: Tamoxifen has been a very effective treatment for breast cancer for several decades, however, at the same time increases the risk of endometrial cancer, especially after prolonged exposure. In addition, tamoxifen has been associated with a higher proportion of unfavorable uterine tumor subtypes (carcinosarcomas and serous adenocarcinomas) with worse survival. We investigated whether endometrial tumors, which developed after prolonged tamoxifen treatment for breast cancer, are genetically different from endometrial tumors without preceding tamoxifen exposure. Experimental design: Array CGH was used on archival formalin-fixed paraffin embedded (FFPE) endometrial tumors to determine genomic aberrations. We compared the genomic profiles of 52 endometrial tumors from breast cancer patients after long-term (>=2 years) tamoxifen use (endometrioid adenocarcinomas n=26, carcinosarcomas n=14 and serous adenocarcinomas n=12) with endometrial tumors from unexposed breast cancer patients (n=45). Genomic profiles were correlated with tamoxifen exposure, tumor subtypes and histopathological characteristics of the endometrial tumors. Results: The common uterine corpus cancers of the endometrioid subtype show few genomic aberrations. Tumors with many genomic aberrations were in general ER-negative. In contrast, carcinosarcomas and serous adenocarcinomas showed many aberrations, however they were indistinguishable from each other. Tumors that developed after prolonged tamoxifen use did not show more or different aberrations than unexposed tumors. This was true for all tumor subtypes. Conclusion: Endometrial carcinomas that develop after prolonged tamoxifen use can not be distinguished from non-users on basis of their tumor genomic profile. 52 endometrial tumors from breast cancer patients after long-term (>=2 years) tamoxifen use (endometrioid adenocarcinomas n=26, carcinosarcomas n=14 and serous adenocarcinomas n=12) and 45 endometrial tumors from unexposed breast cancer patients
2010-06-17 | E-GEOD-16680 | biostudies-arrayexpress
Project description:The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With an extremely poor five-year survival rate of only 15%, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutation spectra from the whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a novel mutational signature in EACs defined by a high prevalence of A to C transversions at Ap*A dinucleotides. Statistical analysis of the exome data identified 26 genes that are mutated at a significant frequency. Of these 26 genes, only four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include several chromatin modifying factors and candidate contributors to EAC: SPG20, TLR4, ELMO1, and DOCK2. Notably, functional analyses of EAC-derived mutations in ELMO1 increase cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis. The study aimed to analyze 150 primary, human esophageal adenocarcinoma samples by whole genome and whole exome sequencing (which will be deposited to dbGAP following the TCGA practice). RNA expression data was used to determine gene expression in 14 of the samples analyzed by whole genome sequencing. No normals were analyzed.
2013-02-11 | E-GEOD-42363 | biostudies-arrayexpress
Project description:With the whole genome SNP array information obtained from tumor and matched normal control, we could evaluate the acquired copy number alterations (CNAs) and uniparental disomies (UPDs) . Here we identified somatic mutations by whole-exome sequencing in 25 NKTCL patients and extended validation through targeted sequencing in an additional 80 cases.
2015-05-29 | GSE69382 | GEO
Project description:The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With an extremely poor five-year survival rate of only 15%, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutation spectra from the whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a novel mutational signature in EACs defined by a high prevalence of A to C transversions at Ap*A dinucleotides. Statistical analysis of the exome data identified 26 genes that are mutated at a significant frequency. Of these 26 genes, only four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include several chromatin modifying factors and candidate contributors to EAC: SPG20, TLR4, ELMO1, and DOCK2. Notably, functional analyses of EAC-derived mutations in ELMO1 increase cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis.
2013-02-11 | GSE42363 | GEO
Project description:This study presents a single-cell RNA sequencing (scRNAseq) analysis of six carcinosarcomas and two normal endometrial samples, profiling over 96,000 cells. By integrating transcriptomic data with inferred copy number variations (CNVs), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH), we resolve the complex cellular architecture and differentiation dynamics of these tumors. We identify distinct lineage-specific programs and uncover heterologous differentiation trajectories—including rhabdomyogenic, osteogenic, and a previously undescribed tenogenic lineage defined by SCX, MKX, and TNMD expression. Our results reveal that carcinosarcomas exhibit multilineage plasticity within their mesenchymal component and highlight the power of single-cell analysis to refine tumor classification and uncover hidden developmental programs.
2025-10-28 | GSE299623 | GEO