scholarly journals Single‐cell transcriptomes reveal heterogeneity of high‐grade serous ovarian carcinoma

2021 ◽  
Vol 11 (8) ◽  
Author(s):  
Qian Hao ◽  
Jiajia Li ◽  
Qinghua Zhang ◽  
Fei Xu ◽  
Bangxiang Xie ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Single Cell ◽  
High Grade ◽  
Serous Ovarian Carcinoma

scholarly journals Multi-omic analysis of subtype evolution and heterogeneity in high-grade serous ovarian carcinoma

2019 ◽  
Author(s):  
Ludwig Geistlinger ◽  
Sehyun Oh ◽  
Marcel Ramos ◽  
Lucas Schiffer ◽  
Rebecca LaRue ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Single Cell ◽  
Genomic Instability ◽  
Tumor Evolution ◽  
High Grade ◽  
Cell Type ◽  
Patient Age ◽  
Immune Infiltration ◽  
Serous Ovarian Carcinoma ◽  
Somatic Aberrations

AbstractMultiple studies have identified transcriptome subtypes of high-grade serous ovarian carcinoma (HGSOC), but these have yet to impact clinical practice. Interpretation and translation of HGSOC subtypes are complicated by tumor evolution and polyclonality accompanied by accumulation of somatic aberrations, varying cell type admixtures, and different tissues of origin. The chronology of HGSOC subtype evolution was examined in the context of these factors by a novel integrative analysis of bulk absolute somatic copy number analysis and gene expression in The Cancer Genome Atlas, complemented by single-cell RNA-seq analysis of six independent tumors. The approach was validated by contrast to soft-tissue sarcoma. Genomic lesions associated with HGSOC subtypes tend to be subclonal, implying subtype divergence at later stages of tumor evolution. Subclonality of recurrent HGSOC alterations is particularly evident for proliferative tumors, characterized by extreme genomic instability, absence of immune infiltration, and greater patient age. In contrast, differentiated tumors are characterized by largely intact genome integrity, high immune infiltration, and younger patient age. We propose an alternative model to discrete subtypes of HGSOC, in which tumors develop from an early differentiated spectrum to a late proliferative spectrum, along a timeline characterized by increasing genomic instability and subclonal expansion. The proposed methods provide a new approach to investigating tumor evolution through multi-omic analysis.Statement of SignificanceThis study proposes a method to infer whether transcriptome-based groupings of tumors differentiate early in carcinogenesis and are therefore potentially appropriate targets for therapy, and demonstrates that this is not the case for high-grade serous ovarian carcinoma (HGSOC). Significant findings for HGSOC include:Tumor purity, ploidy, and subclonality can be reliably inferred from different genomic platforms and show marked differences between subtypesRecurrent DNA alterations are associated with subtypes and tend to occur more frequently in subclonesSingle-cell sequencing of 42,000 tumor cells reveals widespread heterogeneity in tumor cell type composition that drives bulk subtype calls, but demonstrates a lack of intrinsic subtypes among tumor epithelial cellsFindings prompt the dismissal of discrete transcriptome subtypes for HGSOC and replacement by a more realistic model of continuous tumor development that includes mixtures of subclones, accumulation of somatic aberrations, infiltration of immune and stromal cells in proportions correlated with tissue of origin and tumor stage, and evolution between properties previously associated with discrete subtypes

Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma

2015 ◽  
Vol 139 (1) ◽  
pp. 196
Author(s):  
C. Morse ◽  
B. Norquist ◽  
S. Bernards ◽  
M. Harrell ◽  
K. Agnew ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
High Grade ◽  
Molecular Features ◽  
Serous Ovarian Carcinoma

scholarly journals Retinoblastoma pathway deregulatory mechanisms determine clinical outcome in high-grade serous ovarian carcinoma

2013 ◽  
Vol 27 (7) ◽  
pp. 991-1001 ◽  
Author(s):  
Anca Milea ◽  
Sophia HL George ◽  
Donco Matevski ◽  
Haiyan Jiang ◽  
Mary Madunic ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Ovarian Carcinoma ◽  
High Grade ◽  
Serous Ovarian Carcinoma

MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma

2012 ◽  
Vol 228 (2) ◽  
pp. 204-215 ◽  
Author(s):  
Zhaojian Liu ◽  
Jinsong Liu ◽  
Miguel F Segura ◽  
Changshun Shao ◽  
Peng Lee ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
High Grade ◽  
Serous Ovarian Carcinoma

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

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Jennifer Ducie ◽  
Fanny Dao ◽  
Michael Considine ◽  
Narciso Olvera ◽  
Patricia A. Shaw ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Molecular Analysis ◽  
High Grade ◽  
Serous Ovarian Carcinoma

Modeling High-grade serous ovarian carcinoma using a combination of in vivo fallopian tube electroporation and CRISPR-Cas9-mediated genome editing

2021 ◽  
pp. canres.1518.2020
Author(s):  
Katie Teng ◽  
Matthew J Ford ◽  
Keerthana Harwalkar ◽  
YuQi Li ◽  
Alain Sarabia Pacis ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Genome Editing ◽  
Fallopian Tube ◽  
High Grade ◽  
Serous Ovarian Carcinoma

Abstract 741: Characterization of high-grade serous ovarian carcinoma by measuring functional signal transduction pathway activity

2021 ◽  
Author(s):  
Phyllis van der Ploeg ◽  
Laura van Lieshout ◽  
Yvonne Wesseling-Rozendaal ◽  
Anja van de Stolpe ◽  
Diederick Keizer ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Ovarian Carcinoma ◽  
Signal Transduction Pathway ◽  
High Grade ◽  
Transduction Pathway ◽  
Pathway Activity ◽  
Serous Ovarian Carcinoma
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