Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The molecular landscape of homologous recombination deficient, end-stage, high grade serous ovarian cancer

ABSTRACT: High grade serous cancer (HGSC) is frequently characterizsed by homologous recombination (HR) DNA repair deficiency, and while most such tumours are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogating mechanisms of resistance, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. We observed frequent reversion mutations, resistance mechanisms restoring HR by other means, a high frequency of whole-genome duplication (WGD) suggestive of an evolutionary advantage, and global changes in immune composition with evidence of immune escape. Collectively these findings have implications for therapeutic intervention for HR-deficient HGSC.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Whole Body, Stromal Cell

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Thomas Conrads

LAB HEAD: Dr. Elizabeth L Christie

PROVIDER: PXD030034 | Pride | 2023-02-27

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	CASCADE_Sample_Reference_File.xlsx	Xlsx
	Cascade_TMTpro_QEHFX1_060420_4_01.raw	Raw
	Cascade_TMTpro_QEHFX1_060420_4_02.raw	Raw
	Cascade_TMTpro_QEHFX1_060420_4_03.raw	Raw
	Cascade_TMTpro_QEHFX1_060420_4_04.raw	Raw

Items per page:

1 - 5 of 521

Similar Datasets

Proteogenomic Analysis of Enriched Tumor Epithelium Identifies Prognostic Signatures and an Increased Dependency of Homologous Recombination Proficient Cells on BMI1 in High Grade Serous Ovarian Cancer

Project description:Although several proteogenomic analyses of high-grade serous ovarian cancer (HGSOC) have been conducted, these analyses are often dominated by tissues with high levels of tumor cell nuclei (purity), despite low purity being associated with worse outcome. We performed deep proteogenomic profiling of bulk tumor (BT) and laser microdissection (LMD) enriched tumor (ET) and stromal (ST) cell populations from 70 HGSOC patient tumors spanning a broad spectrum of purity. We identified a cluster of patients with longer progression free survival associated with increased immune signatures and validated proteins correlating with tumor infiltrating lymphocytes (TILs) in 65 tumors collected from an independent cohort of 12 HGSOC patients, as well as with overall survival in an additional cohort of 126 HGSOC patients. We identified that homologous recombination deficient (HRD) tumors express transcriptomic and proteomic pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts, including 69 HRD-positive HGSOC tumors. In summary, our proteogenomic analysis provides important new clinically relevant insights into HGSOC tumor cell populations, and have uncovered prognostic proteogenomic alterations correlating with TILs, low tumor purity, as well as expression alterations associated with HRD status and immune infiltration.

2024-03-15 | PXD045417 | Pride

Microenvironment Shapes Small Cell Lung Cancer Neuroendocrine States and Presents Unique Therapeutic Opportunities

Project description:Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intra-tumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the tumor microenvironment (TME) exhibits substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAF) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting an exceptionally poor prognosis. Together, our work provides the first comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLCs adaptable nature, opening possibilities for re-programming the intercellular communications that shape SCLC tumor states.

2024-05-15 | PXD052033 | Pride

ProteoMixture: A Cell Deconvolution Tool for Bulk Tissue Proteomics Data

Project description:Numerous multi-omic investigations of cancer tissue have documented varying and poor pairwise transcript:protein quantitative correlations and most deconvolution tools aiming to predict cell type proportions (cell admixture) have been developed and credentialed using transcript-level data alone. To estimate cell admixture using protein abundance data, we analyzed proteome (and transcriptome data) generated from contrived admixtures of tumor, stroma, and immune cell models or those selectively harvested from the tissue microenvironment by laser microdissection from high grade serous ovarian cancer (HGSOC) tumors. Co-quantified transcripts and proteins performed similarly to estimate stroma and immune cell admixture in two commonly used deconvolution algorithms ESTIMATE and ConsensusTME (r ≥ 0.63). Here we have developed and optimized protein-based signatures to estimate cell admixture proportions and benchmarked these using bulk tumor proteomics data from over 150 HGSOC patients. The optimized protein signatures supporting cell type proportion estimates from bulk tissue proteomic data are available at https://lmdomics.org/ProteoMixture/.

2024-01-12 | PXD044157 | Pride

Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling

Project description:Uterine serous carcinoma (USC) represents only a small proportion of all uterine cancer cases, but patients with this aggressive subtype typically have high rates of chemotherapy resistance, disease recurrence, and constitute a disproportionately high percentage of the deaths. Improving the clinical management of USC is predicated by better characterization of the tumor microenvironment (TME) and the molecular features driving disease pathology. To improve our understanding of intratumoral heterogeneity (ITH) within the USC TME, we investigated proteome and transcriptome alterations in spatially resolved laser microdissection (LMD) enriched cellular subpopulations from nine USC patient tumor tissue specimens. LMD enriched samples were analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), reverse phase protein microarray (RPPA), and targeted RNA-sequencing (RNA-seq).

2024-01-24 | PXD044197 | Pride

Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Expression]

Project description:High grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency, and while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogate the molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole genome duplication, and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that conspire to evade therapy and ultimately overwhelm individual patients.

2022-11-12 | GSE217672 | GEO

The molecular landscape of homologous recombination deficient, end-stage, high grade serous ovarian cancer

| EGAS00001006789 | EGA

Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Methylation]

2022-11-12 | GSE217673 | GEO

High-resolution genome-wide copy number analysis of low grade serous ovarian tumours

Project description:Integration of genomic copy number analysis (Affymetrix SNP6.0 arrays) and oncogenic RAS/RAF mutation status with clinical features and tumour progression. This study found that loss of the 9p and the CDKN2A locus with the most significantly enriched copy number aberration distinguishing serous border tumors from low grade serous carcinomas, suggesting this is a key step to tumor progression. Epithelial tissue from 57 serous borderline tumors (SBTs), 19 low grade serous carcinomas (LGSC)(data for 4 of the carcinomas have previously been submitted to GEO - Series GSE19539) and 355 high grade serous carinomas (HGSC)(TCGA, 2011; GSE19539; and 8 new) were analysed for copy number aberrations using Affymetrix SNP6.0 arrays and normalised SNP6.0 data. Stromal tissue from 38 SBT and 1 HGSC were analysed for copy number aberrations using Affymetrix SNP6.0 arrays. Matching lymphocyte DNA was availabe for 54 SBT, 3 LGSC and 1 HGSC. Sanger sequencing of KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53 mutational hotspots was performed on the epithelial and stromal DNA. This information was then correlated with clinical features of the tumors.

2015-03-01 | E-GEOD-58579 | biostudies-arrayexpress

Classification of High-Grade Serous Ovarian Cancer Using Tumor Morphologic Characteristics

Project description:Despite the similar histologic appearances of high-grade serous ovarian cancers (HGSOCs), clinical observations point to marked differences in their gross appearances. Some patients have numerous small nodules, whereas others have bulkier disease; some patients have widespread disease, whereas others have more localized disease. However, a systematic framework for classifying such gross morphologic differences does not exist. The implementation of a laparoscopic triage algorithm for patients with advanced HGSOC enabled us to prospectively obtain detailed video images of HGSOC that could be analyzed to identify morphologic subtypes. In this study, we aimed to develop and characterize a gross morphologic classification system for HGSOC. Specifically, we assessed whether HGSOC can be reliably divided into distinct gross morphologic subtypes and whether such subtypes have different clinical outcomes and molecular features.

2023-01-27 | PXD031518 | Pride

Evaluation of Tumor Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Project description:Tumor infiltrating lymphocytes (TILs) play a significant role in the tumor microenvironment in high-grade serous ovarian cancer (HGSOC). To better understand the interactions and functions of TILs in HGSOC progression, we performed proteogenomic profiling of TILs in 65 tumors collected from 12 HGSOC patients.

2024-03-15 | PXD045710 | Pride