Characterizing TP53 mutations in ovarian carcinomas with and without concurrent BRCA1 or BRCA2 mutations

Ghezelayagh, Talayeh S.; Pennington, Kathryn P.; Norquist, Barbara M.; Khasnavis, Nithisha; Radke, Marc R.; Kilgore, Mark R.; Garcia, Rochelle L.; Liu, Ming; Katz, Ronit; Leslie, Kimberly K.; Risques, Rosa Ana; Swisher, Elizabeth M.

doi:10.1016/j.ygyno.2020.12.007

Cited by 21 publications

(21 citation statements)

References 38 publications

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“…Moreover, approximately 90% of all patients with serous epithelial ovarian cancer have a TP53 variant. 14 We found a TP53 variant in 59% of patients, which might be explained by tumor heterogeneity. 24 Also, three of our five patients without a pathogenic variant in the surgical specimen had a high-grade serous carcinoma.…”

Section: Discussionmentioning

confidence: 73%

“…Third, we focused on TP53 pathogenic variants as these variants are primarily related to ovarian cancer. 14 …”

Section: Methodsmentioning

confidence: 99%

“…Second, we measured diagnostic accuracy among all patients using the detection of (potentially) pathogenic variants in their surgical sample as gold standard. Third, we focused on TP53 pathogenic variants as these variants are primarily related to ovarian cancer 14…”

Section: Methodsmentioning

confidence: 99%

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Diagnostic accuracy of mutational analysis along the Müllerian tract to detect ovarian cancer

Bommel

Pijnenborg

Putten

et al. 2022

Int J Gynecol Cancer

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ObjectiveOvarian cancer is known for its poor prognosis, which is mainly due to the lack of early symptoms and adequate screening options. In this study we evaluated whether mutational analysis in cervicovaginal and endometrial samples could assist in the detection of ovarian cancer.MethodsIn this prospective multicenter study, we included patients surgically treated for either (suspicion of) ovarian cancer or for a benign gynecological condition (control group). A cervicovaginal self-sample, a Papanicolaou (Pap) smear, a pipelle endometrial biopsy, and the surgical specimen were analyzed for (potentially) pathogenic variants in eight genes (ARID1A,CTNNB1,KRAS,MTOR,PIK3CA,POLE,PTEN, andTP53) using single-molecule molecular inversion probes. Sensitivity and specificity were calculated to assess diagnostic accuracy.ResultsBased on surgical histology, our dataset comprised 29 patients with ovarian cancer and 32 controls. In 83% of the patients with ovarian cancer, somatic (potentially) pathogenic variants could be detected in the final surgical specimen, of which 71% included at least aTP53variant. In 52% of the ovarian cancer patients, such variants could be detected in either the self-sample, Pap smear, or pipelle. The Pap smear yielded the highest diagnostic accuracy with 26% sensitivity (95% CI 10% to 48%). Overall diagnostic accuracy was low and was not improved when includingTP53variants only.ConclusionsMutational analysis in cervicovaginal and endometrial samples has limited accuracy in the detection of ovarian cancer. Future research with cytologic samples analyzed on methylation status or the vaginal microbiome may be relevant.

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Section: Discussionmentioning

confidence: 73%

“…Third, we focused on TP53 pathogenic variants as these variants are primarily related to ovarian cancer. 14 …”

Section: Methodsmentioning

confidence: 99%

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Diagnostic accuracy of mutational analysis along the Müllerian tract to detect ovarian cancer

Bommel

Pijnenborg

Putten

et al. 2022

Int J Gynecol Cancer

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“…The conflicting findings reported in the literature as well as the different survival outcomes of carriers of the same mutations found in this study might indicate the presence of additional factors that modify the risk. Genetic factors such as TP53 mutations [ 28 ] and clinical factors including disease extent that determines initial therapeutic approach [ 29 ] are known to affect survival irrespective of the presence of BRCA1/2 mutations. Whether BRCA1/2 mutation types may affect disease extent at diagnosis, however, remains currently elusive.…”

Section: Discussionmentioning

confidence: 99%

BRCA1/2 Mutation Types Do Not Affect Prognosis in Ovarian Cancer Patients

et al. 2021

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Background: High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline BRCA1/2 mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the BRCA1/2 genes affects the clinical outcome of HGSOC patients. Methods: A total of 51 women with BRCA1 or BRCA2 mutated ovarian cancer were identified. Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: In our study cohort, 35 patients were carriers of germline mutations in BRCA1 and 16 in BRCA2. The median PFS time following completion of the primary therapy was 23.8 months (95% CI 20.1–27.5) and the median OS was 92.9 months (95% CI 69.8–116.1) in all BRCA carriers. After multivariate analysis, no significant association among the location or type of BRCA1/2 mutation with PFS or OS was identified. Notably, significant differences in PFS between carriers of identical mutations in the same BRCA gene were detected. Conclusions: Among HGSOC patients, BRCA1/2 carriers with mutations in different locations of the genes show no significant difference in survival outcomes, in terms of PFS and OS, suggesting the potential effect of other genetic abnormalities and co-contributing risk factors.

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“…Based on their histological and morphological classification OC can be divided in serous, mucinous, endometrial, clear cells and transitional cells (depending on the tissue of origin involved). Moreover, OCs can be divided in type I (low-grade tumor with BRAF and KRAS mutations) or type II (high-grade tumor with a variety of mutations including HOX, PTEN, KRAS, AKT1, BRCA1/2 genes) [5][6][7][8][9][10] and various dysregulated mechanisms underlying the pathology [11][12][13]. An important therapeutic target in OC may be represented by a subpopulation of cells defined as ovarian cancer stem cells (OCSCs) [14] and considered a key factor in cancer initiation, relapse and resistance to therapy [15,16].…”

Section: Introductionmentioning

confidence: 99%

Enhanced ZNF521 expression induces an aggressive phenotype in human ovarian carcinoma cell lines

et al. 2022

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Epithelial ovarian carcinoma (EOC) is the most lethal gynecological tumor, that almost inevitably relapses and develops chemo-resistance. A better understanding of molecular events underlying the biological behavior of this tumor, as well as identification of new biomarkers and therapeutic targets are the prerequisite to improve its clinical management. ZNF521 gene amplifications are present in >6% of OCs and its overexpression is associated with poor prognosis, suggesting that it may play an important role in OC. Increased ZNF521 expression resulted in an enhancement of OC HeyA8 and ES-2 cell growth and motility. Analysis of RNA isolated from transduced cells by RNA-Seq and qRT-PCR revealed that several genes involved in growth, proliferation, migration and tumor invasiveness are differentially expressed following increased ZNF521 expression. The data illustrate a novel biological role of ZNF521 in OC that, thanks to the early and easy detection by RNA-Seq, can be used as biomarker for identification and treatment of OC patients.

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Characterizing TP53 mutations in ovarian carcinomas with and without concurrent BRCA1 or BRCA2 mutations

Cited by 21 publications

References 38 publications

Diagnostic accuracy of mutational analysis along the Müllerian tract to detect ovarian cancer

Diagnostic accuracy of mutational analysis along the Müllerian tract to detect ovarian cancer

BRCA1/2 Mutation Types Do Not Affect Prognosis in Ovarian Cancer Patients

Enhanced ZNF521 expression induces an aggressive phenotype in human ovarian carcinoma cell lines

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