scholarly journals Impact of the APOBEC3A/B deletion polymorphism on risk of ovarian cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liv B. Gansmo ◽  
Nigar Sofiyeva ◽  
Merete Bjørnslett ◽  
Pål Romundstad ◽  
Kristian Hveem ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clear Cell ◽  
Germline Mutations ◽  
Dominant Model ◽  
Deletion Polymorphism ◽  
Hybrid Gene ◽  
Data Set ◽  
Healthy Female ◽  
Potential Cancer ◽  
Reduced Risk

AbstractA germline 29.5-kb deletion variant removes the 3’ end of the APOBEC3A gene and a large part of APOBEC3B, creating a hybrid gene that has been linked to increased APOBEC3 activity and DNA damage in human cancers. We genotyped the APOBEC3A/B deletion in hospital-based samples of 1398 Norwegian epithelial ovarian cancer patients without detected BRCA1/2 germline mutations and compared to 1,918 healthy female controls, to assess the potential cancer risk associated with the deletion. We observed an association between APOBEC3A/B status and reduced risk for ovarian cancer (OR = 0.75; CI = 0.61–0.91; p = 0.003) applying the dominant model. Similar results were found in other models. The association was observed both in non-serous and serous cases (dominant model: OR = 0.69; CI = 0.50–0.95; p = 0.018 and OR = 0.77; CI = 0.62–0.96; p = 0.019, respectively) as well as within high-grade serous cases (dominant model: OR = 0.79; CI = 0.59–1.05). For validation purposes, we mined an available large multinational GWAS-based data set of > 18,000 cases and > 26,000 controls for SNP rs12628403, known to be in linkage disequilibrium with the APOBEC3A/B deletion. We found a non-significant trend for SNP rs12628403 being linked to reduced risk of ovarian cancer in general and similar trends for all subtypes. For clear cell cancers, the risk reduction reached significance (OR = 0.85; CI = 0.69–1.00).

scholarly journals Gene Expression Profile of BRCAness That Correlates With Responsiveness to Chemotherapy and With Outcome in Patients With Epithelial Ovarian Cancer

2010 ◽  
Vol 28 (22) ◽  
pp. 3555-3561 ◽  
Author(s):  
Panagiotis A. Konstantinopoulos ◽  
Dimitrios Spentzos ◽  
Beth Y. Karlan ◽  
Toshiyasu Taniguchi ◽  
Elena Fountzilas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Parp Inhibitor ◽  
Germline Mutations ◽  
Predictive Tool ◽  
Data Set ◽  
Sporadic Disease

Purpose To define a gene expression profile of BRCAness that correlates with chemotherapy response and outcome in epithelial ovarian cancer (EOC). Methods A publicly available microarray data set including 61 patients with EOC with either sporadic disease or BRCA½ germline mutations was used for development of the BRCAness profile. Correlation with platinum responsiveness was assessed in platinum-sensitive and platinum-resistant tumor biopsy specimens from six patients with BRCA germline mutations. Association with poly-ADP ribose polymerase (PARP) inhibitor responsiveness and with radiation-induced RAD51 foci formation (a surrogate of homologous recombination) was assessed in Capan-1 cell line clones. The BRCAness profile was validated in 70 patients enriched for sporadic disease to assess its association with outcome. Results The BRCAness profile accurately predicted platinum responsiveness and mutation status in eight of 10 patient-derived tumor specimens and between PARP-inhibitor sensitivity and resistance in four of four Capan-1 clones. When applied to the 70 patients with sporadic disease, patients with the BRCA-like (BL) profile had improved disease-free survival (34 months v 15 months; log-rank P = .013) and overall survival (72 months v 41 months; log-rank P = .006) compared with patients with a non–BRCA-like (NBL) profile, respectively. The BRCAness profile maintained independent prognostic value in multivariate analysis, which controlled for other known clinical prognostic factors. Conclusion The BRCAness profile correlates with responsiveness to platinum and PARP inhibitors and identifies a subset of sporadic patients with improved outcome. Additional evaluation of this profile as a predictive tool in patients with sporadic EOC is warranted.

scholarly journals Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies

2020 ◽  
Author(s):  
Alice W Lee ◽  
Stacey Rosenzweig ◽  
Ashley Wiensch ◽  
Susan J Ramus ◽  
Usha Menon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Epithelial Ovarian Cancer ◽  
Race And Ethnicity ◽  
Clear Cell ◽  
Ovarian Cancer Risk ◽  
Inverse Association ◽  
Case Control Studies ◽  
Invasive Epithelial Ovarian Cancer ◽  
Reduced Risk

Abstract Background Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. Methods A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. Results Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend < .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. Conclusions Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

scholarly journals Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma

2021 ◽  
Author(s):  
Kosuke Murakami ◽  
Akiko Kanto ◽  
Kazuko Sakai ◽  
Chiho Miyagawa ◽  
Hisamitsu Takaya ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Driver Mutations ◽  
Intratumor Heterogeneity ◽  
Ovarian Clear Cell Carcinoma ◽  
Eutopic Endometrium ◽  
Stromal Component ◽  
Hotspot Mutations

AbstractRecent studies have reported cancer-associated mutations in normal endometrium. Mutations in eutopic endometrium may lead to endometriosis and endometriosis-associated ovarian cancer. We investigated PIK3CA mutations (PIK3CAm) for three hotspots (E542K, E545K, H1047R) in eutopic endometrium in patients with ovarian cancer and endometriosis from formalin-fixed paraffin-embedded specimens by laser-capture microdissection and droplet digital PCR. The presence of PIK3CAm in eutopic endometrial glands with mutant allele frequency ≥ 15% were as follows: ovarian clear cell carcinoma (OCCC) with PIK3CAm in tumors, 20/300 hotspots in 11/14 cases; OCCC without PIK3CAm, 42/78 hotspots in 11/12 cases; high-grade serous ovarian carcinoma, 8/45 hotspots in 3/5 cases; and endometriotic cysts, 5/63 hotspots in 5/6 cases. These rates were more frequent than in noncancer nonendometriosis controls (7/309 hotspots in 5/17 cases). In OCCC without PIK3CAm, 7/12 (58%) cases showed multiple hotspot mutations in the same eutopic endometrial glands. In 3/54 (5.6%) cases, PIK3CAm was found in eutopic endometrial stroma. Multisampling of the OCCC tumors with PIK3CAm showed intratumor heterogeneity in three of eight cases. In two cases, PIK3CAm was detected in the stromal component of the tumor. Homogenous PIK3CAm in the epithelial component of the tumor matched the mutation in eutopic endometrial glands in only one case. Eutopic endometrial glands in ovarian cancer and endometriosis show high frequency of PIK3CAm that is not consistent with tumors, and multiple hotspot mutations are often found in the same glands. While the mutations identified in eutopic endometrium may not be driver mutations in the patient’s cancer, these are still driver mutations but this specific clone has not undergone the requisite steps for the development of cancer.

scholarly journals Multigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer

2015 ◽  
Vol 3 (5) ◽  
pp. 459-466 ◽  
Author(s):  
Yosuke Hirotsu ◽  
Hiroshi Nakagomi ◽  
Ikuko Sakamoto ◽  
Kenji Amemiya ◽  
Toshio Oyama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Panel Analysis ◽  
Breast And Ovarian Cancer ◽  
Repair Genes ◽  
Multigene Panel

scholarly journals High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area

2005 ◽  
Vol 7 (5) ◽  
Author(s):  
Petr Pohlreich ◽  
Michal Zikan ◽  
Jana Stribrna ◽  
Zdenek Kleibl ◽  
Marketa Janatova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Brca1 Gene ◽  
Germline Mutations ◽  
Breast And Ovarian Cancer

Differential expression of ABCF2 protein among different histologic types of epithelial ovarian cancer and in clear cell adenocarcinomas of different organs

2007 ◽  
Vol 38 (1) ◽  
pp. 134-139 ◽  
Author(s):  
Sadako Nishimura ◽  
Hiroshi Tsuda ◽  
Kiyoshi Ito ◽  
Toshiko Jobo ◽  
Nobuo Yaegashi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Differential Expression ◽  
Clear Cell ◽  
Histologic Types

Protein expression levels of excision repair cross-complementation group 1 and xeroderma pigmentosum D correlate with response to platinum-based chemotherapy in the patients with advanced epithelial ovarian cancer

2008 ◽  
Vol 18 (5) ◽  
pp. 1007-1012 ◽  
Author(s):  
K. Lin ◽  
D. Ye ◽  
X. Xie
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Clear Cell ◽  
Excision Repair ◽  
Cell Cancer ◽  
Complementation Group ◽  
Serous Ovarian Cancer ◽  
Expression Levels ◽  
Platinum Based Chemotherapy ◽  
Group 1

This study was undertaken to examine whether there is an association between excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum D (XPD) protein expression levels and response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). The study cohort consisted of 91 consecutive patients suffering from stage III or IV disease of primary EOC from 1999 to 2004 at the Women's Hospital, School of Medicine, Zhejiang University. There were 36 sensitive cases of serous ovarian cancer, 27 resistant cases of serous ovarian cancer, 15 cases of clear cell cancer, and 13 cases with serous ovarian cancer receiving neoadjuvant chemotherapy. The ovarian tissue microsections were stained by standard immunohistochemical techniques to show ERCC1 and XPD protein expression levels. In resistance group of serous ovarian cancer, ERCC1 and XPD protein expression levels were significantly higher than those of sensitivity group, and after receiving neoadjuvant chemotherapy, they showed 23% and 32% higher than before. Meanwhile, their levels of clear cell cancer group were significantly higher than serous ovarian cancer group's. Upregulation of ERCC1 and XPD protein expression was associated with resistance process to platinum-based chemotherapy in advanced EOC. This study provided evidence that differences of nucleotide excision repair–related genes expression may have an effect on the observed differences in clinical behavior of EOC

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