The somatic and germline mutation pattern of 21 hereditary ovarian cancer genes in 62 Chinese ovarian cancers

2019 ◽  
Vol 154 ◽  
pp. 272
Author(s):  
L. Li ◽  
X. Meng ◽  
C. Lin ◽  
D. Shao ◽  
Y. Xiong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Germline Mutation ◽  
Cancer Genes ◽  
Hereditary Ovarian Cancer ◽  
Ovarian Cancers ◽  
Mutation Pattern

scholarly journals Management of hereditary ovarian cancer

2011 ◽  
Vol 152 (40) ◽  
pp. 1596-1608 ◽  
Author(s):  
József Gábor Joó ◽  
Szabolcs Ládi ◽  
B. Zsolt Nagy ◽  
Zoltán Langmár
Keyword(s):  
Ovarian Cancer ◽  
Hereditary Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Ovarian Cancers ◽  
Brca2 Mutations ◽  
Histological Phenotype ◽  
Brca1 Brca2 ◽  
Brca1 And Brca2 Mutations ◽  
High Level ◽  
Associated Tumors

Mutations in BRCA1 and BRCA2 genes account for the majority of hereditary breast and ovarian cancers. Approximately 10% of cases of ovarian cancer are due to germline mutations in BRCA1 and BRCA2. Ovarian cancer associated with BRCA1 and BRCA2 mutations has a distinct histological phenotype. This type of cancer is predominantly of serous or endometrioid histology and is high grade. Patients with BRCA1 or BRCA2 mutations should be offered risk-reducing salpingo-oophorectomy by age 40 years, or when childbearing is complete. Nowadays there are no differences between the treatments provided for sporadic and hereditary ovarian cancer, although there are indications that targeted therapy is effective in women with BRCA1/BRCA2-associated tumors. Retrospective studies reveal a high level of sensitivity to platinum agents in BRCA-associated tumors and initial trials show good efficacy and tolerability for polyADP-ribose polymerase inhibitors in mutation carriers with advanced ovarian cancers. These agents might also potentially be used in chemoprevention. Authors review the current management of hereditary ovarian cancer. Orv. Hetil., 2011, 152, 1596–1608.

Evaluation of BRCA1/2 and homologous recombination defects in ovarian cancer and impact on clinical outcomes.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5511-5511 ◽  
Author(s):  
Melinda S. Yates ◽  
Kirsten Timms ◽  
Molly S Daniels ◽  
Holly D. Oakley ◽  
Mark F. Munsell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Germline Mutation ◽  
Large Scale ◽  
Recurrent Ovarian Cancer ◽  
State Transitions ◽  
Cancer Genes ◽  
The Impact

5511 Background: Recent studies show that germline or somatic BRCA1/2 mutations and homologous recombination (HR) defects can be used to predict response to PARP inhibitors in recurrent ovarian cancer. However, the impact of defects in BRCA1/2 and HR genes on overall clinical outcomes are not yet defined for patients undergoing neoadjuvant chemotherapy (NACT) versus upfront surgical debulking (USD). Methods: Previously untreated ovarian cancer patients were prospectively enrolled under approved IRB protocol. Germline and tumor BRCA1/2 mutation testing and methylation were analyzed when sufficient tumor and blood was available. Mutation in 21 additional hereditary cancer genes (including HR genes) was also evaluated. Tumor HR defects were scored on LOH, telomeric allelic imbalance, and large-scale state transitions (as previously described). Presence of germline or somatic BRCA1/2 mutations, BRCA1 methylation, HR score ≥42, or germline mutation in other HR genes were defined together as HRD positive. Results: Of 299 enrolled patients, 129 (43%) received USD and 170 (57%) received NACT. Patients receiving USD had better outcomes compared to NACT, including overall survival (OS, 65.8 vs 45.2 months, p = 0.0003) and event free survival (EFS, 24.8 vs 15.6 months, p < 0.0001). In the overall cohort, EFS was significantly longer for HRD positive patients vs HRD negative (20.5 vs 16.3 months, p = 0.0268). Patients with somatic and germline BRCA1/2 mutations had longer OS vs BRCA1/2 negative (65.3 vs 46.1 months, p = 0.0403). Overall outcomes were worse in NACT compared to USD, but impact of BRCA1/2 mutations and HR defects was stronger in this group. NACT patients with any HR defect had longer EFS (19.7 vs 14.5 months, p = 0.0247). NACT patients with BRCA1/2 germline mutations had longer OS (65.3 vs 38.3 months, p = 0.0230). NACT patients with BRCA1/2 germline mutation had longer EFS (22.6 vs 14.6 months, p = 0.0047). OS and EFS in USD patients were significantly changed based on only debulking status; mutation or HR status did not have a statistically significant effect. Conclusions: While HR defects and BRCA1/2 mutations influence overall outcomes for ovarian cancer patients, the impact is stronger in NACT compared to USD.

scholarly journals A radiomic nomogram based on arterial phase of CT for differential diagnosis of ovarian cancer

2021 ◽  
Author(s):  
Yumin Hu ◽  
Qiaoyou Weng ◽  
Haihong Xia ◽  
Tao Chen ◽  
Chunli Kong ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Ovarian Cancer ◽  
Clinical Data ◽  
Arterial Phase ◽  
Multivariable Logistic Regression Analysis ◽  
Clinical Factors ◽  
Good Discrimination ◽  
Training Cohort ◽  
Ovarian Cancers ◽  
Radiomics Signature

Abstract Purpose To develop and validate a radiomic nomogram based on arterial phase of CT to discriminate the primary ovarian cancers (POCs) and secondary ovarian cancers (SOCs). Methods A total of 110 ovarian cancer patients in our hospital were reviewed from January 2010 to December 2018. Radiomic features based on the arterial phase of CT were extracted by Artificial Intelligence Kit software (A.K. software). The least absolute shrinkage and selection operation regression (LASSO) was employed to select features and construct the radiomics score (Rad-score) for further radiomics signature calculation. Multivariable logistic regression analysis was used to develop the predicting model. The predictive nomogram model was composed of rad-score and clinical data. Nomogram discrimination and calibration were evaluated. Results Two radiomic features were selected to build the radiomics signature. The radiomics nomogram that incorporated 2 radiomics signature and 2 clinical factors (CA125 and CEA) showed good discrimination in training cohort (AUC 0.854), yielding the sensitivity of 78.8% and specificity of 90.7%, which outperformed the prediction model based on radiomics signature or clinical data alone. A visualized differential nomogram based on the radiomic score, CEA, and CA125 level was established. The calibration curve demonstrated the clinical usefulness of the proposed nomogram. Conclusion The presented nomogram, which incorporated radiomic features of arterial phase of CT with clinical features, could be useful for differentiating the primary and secondary ovarian cancers.

scholarly journals Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs

2021 ◽  
Vol 7 (9) ◽  
pp. eabb0737
Author(s):  
Zhengnan Yang ◽  
Wei Wang ◽  
Linjie Zhao ◽  
Xin Wang ◽  
Ryan C. Gimple ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Phenotype ◽  
Ovarian Cancers ◽  
Novel Approach

Ovarian cancer represents a highly lethal disease that poses a substantial burden for females, with four main molecular subtypes carrying distinct clinical outcomes. Here, we demonstrated that plasma cells, a subset of antibody-producing B cells, were enriched in the mesenchymal subtype of high-grade serous ovarian cancers (HGSCs). Plasma cell abundance correlated with the density of mesenchymal cells in clinical specimens of HGSCs. Coculture of nonmesenchymal ovarian cancer cells and plasma cells induced a mesenchymal phenotype of tumor cells in vitro and in vivo. Phenotypic switch was mediated by the transfer of plasma cell–derived exosomes containing miR-330-3p into nonmesenchymal ovarian cancer cells. Exosome-derived miR-330-3p increased expression of junctional adhesion molecule B in a noncanonical fashion. Depletion of plasma cells by bortezomib reversed the mesenchymal characteristics of ovarian cancer and inhibited in vivo tumor growth. Collectively, our work suggests targeting plasma cells may be a novel approach for ovarian cancer therapy.

scholarly journals Colorectal Cancer Risk in Women with Gynecologic Cancers—A Population Retrospective Cohort Study

2021 ◽  
Vol 10 (14) ◽  
pp. 3127
Author(s):  
Szu-Chia Liao ◽  
Hong-Zen Yeh ◽  
Chi-Sen Chang ◽  
Wei-Chih Chen ◽  
Chih-Hsin Muo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Cohort Study ◽  
Cancer Patients ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Gynecologic Cancer ◽  
Ovarian Cancers ◽  
Increased Risk

We conducted a retrospective cohort study to evaluate the subsequent colorectal cancer (CRC) risk for women with gynecologic malignancy using insurance claims data of Taiwan. We identified patients who survived cervical cancer (N = 25,370), endometrial cancer (N = 8149) and ovarian cancer (N = 7933) newly diagnosed from 1998 to 2010, and randomly selected comparisons (N = 165,808) without cancer, matched by age and diagnosis date. By the end of 2011, the incidence and hazard ratio (HR) of CRC were estimated. We found that CRC incidence rates were 1.26-, 2.20-, and 1.61-fold higher in women with cervical, endometrial and ovarian cancers, respectively, than in comparisons (1.09/1000 person–years). The CRC incidence increased with age. Higher adjusted HRs of CRC appeared within 3 years for women with endometrial and ovarian cancers, but not until the 4th to 7th years of follow up for cervical cancer survivals. Cancer treatments could reduce CRC risks, but not significantly. However, ovarian cancer patients receiving surgery alone had an incidence of 3.33/1000 person–years for CRC with an adjusted HR of 3.79 (95% CI 1.11–12.9) compared to patients without any treatment. In conclusion, gynecologic cancer patients are at an increased risk of developing CRC, sooner for those with endometrial or ovarian cancer than those with cervical cancer.

scholarly journals Genomic, Transcriptomic, and Functional Alterations in DNA Damage Response Pathways as Putative Biomarkers of Chemotherapy Response in Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1420
Author(s):  
Sweta Sharma Saha ◽  
Lucy Gentles ◽  
Alice Bradbury ◽  
Dominik Brecht ◽  
Rebecca Robinson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Personalised Medicine ◽  
Primary Cultures ◽  
The Cancer Genome Atlas ◽  
Chemotherapy Response ◽  
Chemotherapy Drugs ◽  
Ovarian Cancers ◽  
Damage Response

Defective DNA damage response (DDR) pathways are enabling characteristics of cancers that not only can be exploited to specifically target cancer cells but also can predict chemotherapy response. Defective Homologous Recombination Repair (HRR) function, e.g., due to BRCA1/2 loss, is a determinant of response to platinum agents and PARP inhibitors in ovarian cancers. Most chemotherapies function by either inducing DNA damage or impacting on its repair but are generally used in the clinic unselectively. The significance of HRR and other DDR pathways in determining response to several other chemotherapy drugs is not well understood. In this study, the genomic, transcriptomic and functional analysis of DDR pathways in a panel of 14 ovarian cancer cell lines identified that defects in DDR pathways could determine response to several chemotherapy drugs. Carboplatin, rucaparib, and topotecan sensitivity were associated with functional loss of HRR (validated in 10 patient-derived primary cultures) and mismatch repair. Two DDR gene expression clusters correlating with treatment response were identified, with PARP10 identified as a novel marker of platinum response, which was confirmed in The Cancer Genome Atlas (TCGA) ovarian cancer cohort. Reduced non-homologous end-joining function correlated with increased sensitivity to doxorubicin, while cells with high intrinsic oxidative stress showed sensitivity to gemcitabine. In this era of personalised medicine, molecular/functional characterisation of DDR pathways could guide chemotherapy choices in the clinic allowing specific targeting of ovarian cancers.

Limitations of direct-to-consumer (DTC) genetic testing for hereditary breast and ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10515-10515
Author(s):  
Neelam Vijay Desai ◽  
Elizabeth Dominic Barrows ◽  
Sarah M. Nielsen ◽  
Kathryn E. Hatchell ◽  
Edward D. Esplin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Clinical Indication ◽  
Ovarian Cancer Risk ◽  
Cancer Genes ◽  
Primary Analysis ◽  
Risk Genes ◽  
Group 3 ◽  
Group 5

10515 Background: With the advent of DTC genetic testing, individuals have access to genetic testing without input from a healthcare professional. DTC testing now exists for the 3 Ashkenazi Jewish (AJ) BRCA1/2 founder variants. DTC testing may provide false reassurance to individuals that they do not carry a pathogenic or likely pathogenic variant (PLPV) in BRCA1/2 or other cancer-risk genes. Methods: Multi-panel genetic testing was performed in 348,692 individuals for a clinical indication of hereditary breast/ovarian cancer (Clinical cohort) and 7,636 self-referred ostensibly healthy individuals (Healthy cohort) by a clinical testing laboratory. The primary analysis evaluated PLPVs for Group 1 genes: BRCA1/2 AJ founder variants and Group 2: full sequence BRCA1/2. Secondary analyses assessed PLPVs in Group 3: high-risk breast cancer genes ( BRCA1/2, CDH1, PALB2, PTEN, STK11, TP53), Group 4: all breast or ovarian cancer-risk genes (Group 3 genes plus ATM, BARD1, BRIP1, truncating CHEK2, EPCAM, MLH1, MSH2/6, NF1, PMS2, RAD51C/D) and Group 5: 41 cancer-risk genes; these analyses were limited to participants who tested for all 41 genes. Potentially mosaic variants were excluded. Results: Table illustrates PLPVs found in both cohorts. The BRCA1/2 AJ founder variants account for only ̃11% (1513/13,987) and ̃30% (19/64) of the BRCA PLPVs in the Clinical and Healthy cohorts, respectively. Even among AJ individuals, testing only for the 3 founder variants will miss ̃10% (52/513) of all BRCA1/2 PLPVs. Evaluating only the BRCA AJ founder variants missed a higher percentage of PLPVs in other cancer-risk genes. Conclusions: The 3 BRCA1/2 AJ founder variants analyzed by DTC testing account for a small fraction of PLPVs in cancer-risk genes in the general population, and miss 10% of BRCA PLPVs even among AJ individuals. Greater public education is needed to dispel the misconception that DTC tests are equivalent to clinical assessment and comprehensive genetic testing. PLPVs identified in Clinical and Healthy Cohorts.[Table: see text]

Hereditary ovarian cancer

1997 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Amelia A. Langston ◽  
Elaine A. Ostrander
Keyword(s):  
Ovarian Cancer ◽  
Hereditary Ovarian Cancer
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