Early Detection of High-grade Tubal Serous Carcinoma in Women at Low Risk for Hereditary Breast and Ovarian Cancer Syndrome by Systematic Examination of Fallopian Tubes Incidentally Removed During Benign Surgery

2014 ◽  
Vol 38 (6) ◽  
pp. 729-742 ◽  
Author(s):  
Joseph T. Rabban ◽  
Karuna Garg ◽  
Beth Crawford ◽  
Lee-may Chen ◽  
Charles J. Zaloudek
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Low Risk ◽  
Serous Carcinoma ◽  
High Grade ◽  
Fallopian Tubes ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Systematic Examination

scholarly journals The Ovary Is an Alternative Site of Origin for High-Grade Serous Ovarian Cancer in Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (6) ◽  
pp. 1975-1981 ◽  
Author(s):  
Jaeyeon Kim ◽  
Donna M. Coffey ◽  
Lang Ma ◽  
Martin M. Matzuk
Keyword(s):  
Ovarian Cancer ◽  
Double Mutant ◽  
P53 Mutation ◽  
Mutant Mice ◽  
Serous Carcinoma ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Fallopian Tubes ◽  
Double Knockout ◽  
Triple Mutant

Abstract Although named “ovarian cancer,” it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53R172H, into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53R172H-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice.

scholarly journals “It wasn't just for me”: Motivations and implications of genetic testing for women at a low risk of hereditary breast and ovarian cancer syndrome

2020 ◽  
Vol 29 (8) ◽  
pp. 1303-1311
Author(s):  
Gulvir Gill ◽  
Catherine Beard ◽  
Kirsty Storey ◽  
Shelby Taylor ◽  
Adrienne Sexton
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Low Risk ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer

scholarly journals Targeting progesterone signaling prevents metastatic ovarian cancer

2020 ◽  
Vol 117 (50) ◽  
pp. 31993-32004
Author(s):  
Olga Kim ◽  
Eun Young Park ◽  
Sun Young Kwon ◽  
Sojin Shin ◽  
Robert E. Emerson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Deleterious Mutation ◽  
Peritoneal Metastases ◽  
Cancer Development ◽  
Serous Carcinoma ◽  
Cancer Type ◽  
High Grade ◽  
Primary Tumors ◽  
High Risk Populations ◽  
Genetic Deletion

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

scholarly journals BARD1 Autoantibody Blood Test for Early Detection of Ovarian Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 969
Author(s):  
Maxim Pilyugin ◽  
Magda Ratasjka ◽  
Maciej Stukan ◽  
Nicole Concin ◽  
Robert Zeillinger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Menopausal Status ◽  
Clinical Samples ◽  
Average Risk ◽  
Healthy Controls ◽  
Cancer Antigen 125 ◽  
Cancer Syndrome ◽  
Ovarian Cancer Screening

Background: Ovarian cancer (OC) is the most lethal gynaecological cancer. It is often diagnosed at an advanced stage with poor chances for successful treatment. An accurate blood test for the early detection of OC could reduce the mortality of this disease. Methods: Autoantibody reactivity to 20 epitopes of BARD1 and concentration of cancer antigen 125 (CA125) were assessed in 480 serum samples of OC patients and healthy controls. Autoantibody reactivity and CA125 were also tested for 261 plasma samples of OC with or without mutations in BRCA1/2, BARD1, or other predisposing genes, and healthy controls. Lasso statistic regression was applied to measurements to develop an algorithm for discrimination between OC and controls. Findings and interpretation: Measurement of autoantibody binding to a number of BARD1 epitopes combined with CA125 could distinguish OC from healthy controls with high accuracy. This BARD1-CA125 test was more accurate than measurements of BARD1 autoantibody or CA125 alone for all OC stages and menopausal status. A BARD1-CA125-based test is expected to work equally well for average-risk women and high-risk women with hereditary breast and ovarian cancer syndrome (HBOC). Although these results are promising, further data on well-characterised clinical samples shall be used to confirm the potential of the BARD1-CA125 test for ovarian cancer screening.

scholarly journals Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 547
Author(s):  
Iolia Akaev ◽  
Siavash Rahimi ◽  
Olubukola Onifade ◽  
Francis John Edward Gardner ◽  
David Castells-Rufas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Unknown Origin ◽  
Parp Inhibitors ◽  
Serous Carcinoma ◽  
High Grade ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Epithelial Cancers ◽  
Pathogenic Variants ◽  
Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

scholarly journals Precision Oncology of High-Grade Ovarian Cancer Defined through Targeted Sequencing

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5240
Author(s):  
Sandra Wessman ◽  
Beatriz Bohorquez Fuentes ◽  
Therese Törngren ◽  
Anders Kvist ◽  
Georgia Kokaraki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Characterization ◽  
Parp Inhibitor ◽  
Clinical Information ◽  
Undifferentiated Carcinoma ◽  
Serous Carcinoma ◽  
Precision Oncology ◽  
High Grade ◽  
Histologic Diagnosis ◽  
Germline Testing

Background: We examined whether molecular characterization of high-grade epithelial ovarian cancer can inform the diagnosis and/or identify potential actionable targets. Methods: All of the consecutively sequenced high-grade ovarian tumours with consent between 2014 until 2019 were included. A total of 274 tumours underwent next generation sequencing using a targeted panel. Results: Patients with high-grade ovarian epithelial cancer were consented to prospective molecular characterization. Clinical information was extracted from their medical record. Tumour DNA was subjected to sequencing, and selected patients received PARP inhibitor therapy. Conclusions: Tumours from 274 women were sequenced, including high-grade serous carcinoma (n = 252), clear cell carcinoma (n = 4), carcinosarcoma (n = 9), endometrioid carcinoma (n = 3), undifferentiated carcinoma (n = 1), and mixed tumours (n = 5). Genomic profiling did not influence histologic diagnosis. Mutations were identified in TP53, BRCA1, BRCA2, as well as additional homologous recombination repair pathway genes BARD1, ATR, CHEK2, PALB2, RAD51D, RAD50, SLX4, FANCA, RAD51C, and RAD54L. In addition, mutations in PTEN and CDKN2A were identified. Several somatic mutations with implications for germline testing were identified, including RMI1, STK11, and CDH1. Germline testing identified 16 previously unknown BRCA1/2 carriers. Finally, 20 patients were treated with the PARP inhibitor olaparib based on the sequencing results.

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