scholarly journals Morphological basics of ovarian tumor histogenesis

2020 ◽  
Vol 16 (1) ◽  
pp. 78-84
Author(s):  
F. V. Novikov ◽  
I. S. Luneva ◽  
E. S. Mishina ◽  
M. V. Mnikhovich
Keyword(s):  
Stem Cells ◽  
Ovarian Carcinoma ◽  
Fallopian Tube ◽  
Ovarian Tumor ◽  
Surface Epithelium ◽  
High Grade ◽  
Serous Ovarian Carcinoma ◽  
New Hypothesis ◽  
Tumor Histogenesis

Researches about the origin of epithelial ovarian tumors (EOT) tell about its conception. In particular, the origin of cells from the secondary mullerian system. Also, in the article we examine a new hypothesis that the EOT originates in the epithelium of the fallopian tube (FT) – their contradictoriness and new conception of “precursor escape” which tries to explain the phenomenon of injuries absence of FT by high-grade serous ovarian carcinoma. Carcinogenesis from the FT represents great opportunities for reassessment of clinical data. Also, the article represents the role of stem cells of the surface epithelium of ovaries and FT in EOT carcinogenesis.

scholarly journals Both fallopian tube and ovarian surface epithelium are cells-of-origin for high-grade serous ovarian carcinoma

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shuang Zhang ◽  
Igor Dolgalev ◽  
Tao Zhang ◽  
Hao Ran ◽  
Douglas A. Levine ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Fallopian Tube ◽  
Cell Types ◽  
Ovarian Surface Epithelium ◽  
Genetically Engineered ◽  
Surface Epithelium ◽  
High Grade ◽  
Cell Of Origin ◽  
Ovarian Surface ◽  
Serous Ovarian Carcinoma

AbstractThe cell-of-origin of high grade serous ovarian carcinoma (HGSOC) remains controversial, with fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) both considered candidates. Here, by using genetically engineered mouse models and organoids, we assessed the tumor-forming properties of FTE and OSE harboring the same oncogenic abnormalities. Combined RB family inactivation and Tp53 mutation in Pax8 + FTE caused Serous Tubal Intraepithelial Carcinoma (STIC), which metastasized rapidly to the ovarian surface. These events were recapitulated by orthotopic injection of mutant FTE organoids. Engineering the same genetic lesions into Lgr5 + OSE or OSE-derived organoids also caused metastatic HGSOC, although with longer latency and lower penetrance. FTE- and OSE-derived tumors had distinct transcriptomes, and comparative transcriptomics and genomics suggest that human HGSOC arises from both cell types. Finally, FTE- and OSE-derived organoids exhibited differential chemosensitivity. Our results comport with a dualistic origin for HGSOC and suggest that the cell-of-origin might influence therapeutic response.

scholarly journals Both Fallopian Tube and Ovarian Surface Epithelium Can Act as Cell-of-Origin for High Grade Serous Ovarian Carcinoma

2018 ◽  
Author(s):  
Shuang Zhang ◽  
Tao Zhang ◽  
Igor Dolgalev ◽  
Hao Ran ◽  
Douglas A. Levine ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Fallopian Tube ◽  
Ovarian Surface Epithelium ◽  
Genetically Engineered ◽  
Differential Sensitivity ◽  
Surface Epithelium ◽  
High Grade ◽  
Cell Of Origin ◽  
Ovarian Surface ◽  
Serous Ovarian Carcinoma

ABSTRACTThe cell-of-origin of high grade serous ovarian carcinoma (HGSOC) remains controversial, with fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) each suggested as candidates. Here, by using genetically engineered mouse models and novel organoid systems, we assessed the tumor-forming capacity and properties of FTE and OSE harboring the same oncogenic abnormalities. Combined RB family inactivation (via T121 expression) and Tp53 mutation in Pax8+ FTE caused transformation to Serous Tubal Intraepithelial Carcinoma (STIC), which rapidly metastasized to the ovarian surface. This mouse model was recapitulated by FTE organoids, which, upon orthotopic injection, generated widely metastatic HGSOC. The same genetic lesions in Lgr5+ OSE cells or organoids also caused metastatic HGSOC, although with longer latency and lower penetrance. Comparative transcriptome analysis was consistent with different human HGSOCs arising from FTE and OSE. Furthermore, FTE- and OSE-derived organoids showed differential sensitivity to HGSOC chemotherapeutics. Our results comport with a dualistic origin for HGSOC and suggest the cell-of-origin could influence therapeutic response.SIGNIFICANCEThe cell-of-origin for high grade serous ovarian carcinoma (HGSOC) has been controversial. By generating novel GEMMs and organoid models with the same oncogenic defects, we demonstrate that HGSOC can originate from either fallopian tube epithelium (FTE) or ovarian surface epithelium (OSE). Importantly, FTE- and OSE-derived tumors differ significantly in biologic properties.

scholarly journals Most commonly mutated genes in High Grade Serous Ovarian Carcinoma are nonessential for ovarian surface epithelial stem cell transformation

2020 ◽  
Author(s):  
Robert J. Yamulla ◽  
Shreya Nalubola ◽  
Andrea Flesken-Nikitin ◽  
Alexander Yu. Nikitin ◽  
John C. Schimenti
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ovarian Carcinoma ◽  
Gynecological Cancer ◽  
The Cancer Genome Atlas ◽  
Research Network ◽  
Surface Epithelium ◽  
High Grade ◽  
Ovarian Surface ◽  
Serous Ovarian Carcinoma

AbstractHigh grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological cancer and the 5th leading cause of cancer-related deaths of women in the USA. Disease-associated mutations have been identified by the Cancer Genome Atlas Research Network. However, aside from mutations in TP53 or alterations in the RB1 pathway that are extremely common in HGSOC, the contributions of other mutation combinations have been difficult to assess experimentally or with genomic data alone. Previous research identified ALDH+ stem cells of the ovarian surface epithelium (OSE) as one of the putative cells of HGSOC origin. Here, we performed combinatorial CRISPR mutagenesis of 20 putative HGSOC driver genes to identify mutation combinations that transformed OSE stem cells (OSE-SC) and non-stem cells (OSE-NS). Overrepresented mutations and mutation combinations were identified in all transformants and were investigated directly in targeted assays. Our results support the OSE stem cell theory of HGSOC initiation and suggest that most commonly mutated genes in HGSOC have no effect on OSE-SC transformation initiation. We suggest a model in which combined disruption of RB1 and PTEN, in addition to TP53 deficiency, constitutes a core set of mutations required for efficient transformation in vitro. A few previously uncharacterized mutation combinations further enhanced transformation but may have done so via TP53-related mechanisms. Together, our results identify mutation combinations that are critical for OSE-SC transformation and may contribute to more accurate modeling of HGSOC development. Our cancer driver screening methodology may also serve as a model for high throughput functional assessment of commonly mutated genes uncovered in other cancers by large scale sequencing.

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

scholarly journals Low RAP80 mRNA Expression Correlates with Shorter Survival in Sporadic High-Grade Serous Ovarian Carcinoma

2017 ◽  
Vol 32 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Margarita Romeo ◽  
Niki Karachaliou ◽  
Imane Chaid ◽  
Cristina Queralt ◽  
Itziar De Aguirre ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Figo Stage ◽  
High Grade ◽  
Platinum Compounds ◽  
Serous Ovarian Carcinoma ◽  
Platinum Based Chemotherapy

Objective Homologous recombination (HR) is frequently impaired in sporadic high-grade serous ovarian carcinoma (sHGSOC) due to deficiencies in BRCA1/2 genes, a situation associated with hypersensitivity to platinum compounds. Alterations in other genes can also cause HR deficiency. Preclinical data show that RAP80 is an HR–pathway-related gene that influences BRCA1 activity. RAP80 has been reported to affect outcome in some solid neoplasms. This study investigates the role of RAP80 in sHGSOC survival. Methods mRNA expression of RAP80 was analyzed in tumor samples from 35 patients who postoperatively received standard platinum-based chemotherapy. The effects of RAP80 expression on progression-free survival (PFS) and overall survival (OS) were examined by means of Cox regressions. The clinical variables known to have prognostic value (FIGO stage, residual disease at surgery, and debulking surgery) were included as covariates in the analysis. BRCA1 was analyzed given the moderate correlations with RAP80. Results Median follow-up, PFS and OS were 61.3, 20.2 and 62.8 months, respectively. Low RAP80 expression levels were associated with shorter PFS ( HR = 1.449, p = 0.007) and OS ( HR = 1.331, p = 0.047). Conclusions This is the first study to show a potential prognostic role of RAP80 expression in patients with HGSOC. The results suggest that HR deficiency due to low RAP80 expression is not associated with hypersensitivity to platinum compounds in sHGSOC.

scholarly journals The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma

Oncotarget ◽  
2015 ◽  
Vol 6 (31) ◽  
pp. 31593-31603 ◽  
Author(s):  
Euan A. Stronach ◽  
Paula Cunnea ◽  
Christina Turner ◽  
Tankut Guney ◽  
Radhika Aiyappa ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Interleukin 8 ◽  
High Grade ◽  
Serous Ovarian Carcinoma
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