Germline mutations in cancer susceptibility genes in high grade serous ovarian cancer in Serbia

Krivokuća, Ana; Boljević, Ivana; Jovandic, Stevo; Magić, Zvonko; Mandić, Aljoša; Tomašević, Zorica; Branković-Magić, Mirjana

doi:10.1038/s10038-019-0562-z

Cited by 12 publications

(9 citation statements)

References 43 publications

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“…Mutations in NF1 were absent and were extremely rare in CDH1 and PTEN, just like STK11 mutations found in a patient with nonepithelial OC, a characteristic Peutz-Jeghers syndrome manifestation [9]. Altogether, the high overall frequency of mutations in OC predisposition genes in our study is in agreement with some previous studies [4][5][6]28] and may contribute to a high OC incidence in our population.…”

Section: Discussionsupporting

confidence: 92%

“…The BRCA1 and BRCA2 mutations, present in 84.0% of all mutation carriers, were by far the most frequent alterations found in 17.9% and 7.4% of our patients, respectively. Mutations in other eight genes leaded by RAD51C/RAD51D/BRIP1 affected additional 5.0% of patients, as shown also by others recently [5,6,22]. Germline mutations in Lynch syndrome genes together associated with high OC risk.…”

Section: Discussionmentioning

confidence: 61%

“…Genetic predisposition for OC is unusually high and is reported in up to 25% of cases [4][5][6]. The most frequent germline mutations affect the BRCA1 and BRCA2 genes, conferring 24% and 8.4% OC lifetime risks, respectively [7].…”

Section: Introductionmentioning

confidence: 99%

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Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer

Lhotová

Zemánková

Vočka

et al. 2020

Cancers

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Ovarian cancer (OC) is the deadliest gynecologic malignancy with a substantial proportion of hereditary cases and a frequent association with breast cancer (BC). Genetic testing facilitates treatment and preventive strategies reducing OC mortality in mutation carriers. However, the prevalence of germline mutations varies among populations and many rarely mutated OC predisposition genes remain to be identified. We aimed to analyze 219 genes in 1333 Czech OC patients and 2278 population-matched controls using next-generation sequencing. We revealed germline mutations in 18 OC/BC predisposition genes in 32.0% of patients and in 2.5% of controls. Mutations in BRCA1/BRCA2, RAD51C/RAD51D, BARD1, and mismatch repair genes conferred high OC risk (OR > 5). Mutations in BRIP1 and NBN were associated with moderate risk (both OR = 3.5). BRCA1/2 mutations dominated in almost all clinicopathological subgroups including sporadic borderline tumors of ovary (BTO). Analysis of remaining 201 genes revealed somatic mosaics in PPM1D and germline mutations in SHPRH and NAT1 associating with a high/moderate OC risk significantly; however, further studies are warranted to delineate their contribution to OC development in other populations. Our findings demonstrate the high proportion of patients with hereditary OC in Slavic population justifying genetic testing in all patients with OC, including BTO.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 61%

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Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer

Lhotová

Zemánková

Vočka

et al. 2020

Cancers

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show abstract

“…Since 2008, we have performed tumor-specific molecular analysis of hot spot mutation regions of relevant genes for selection of targeted therapies in various cancer subtypes (EGFR for tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer, KRAS/NRAS for EGFR inhibitors in metastatic colorectal cancer, BRAF for TKIs in metastatic melanoma) [4][5][6][7]. Since 2016 we have also routinely performed BRCA1/2 germline and somatic testing for platinum-sensitive high-grade serous ovarian cancer patients (HGSOC) [8]. Germline and somatic BRCA1/2 mutations are associated with higher sensitivity both to platinum chemotherapy and PARP inhibitors allowing us to use them as important biomarkers for therapy selection in recurrent ovarian cancer [9].…”

Section: 1pharmacogenomics -Genetic Testing For Targeted Therapy Smentioning

confidence: 99%

Exploring the real-world effect of the SARS-CoV-2 pandemic on the molecular diagnostics for cancer patients and high-risk individuals

Čavić

Krivokuća

Boljević

et al. 2020

Expert Review of Molecular Diagnostics

Self Cite

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“…The PI3K/AKT signaling pathway has been shown to be constitutively activated in BRCA1-defective cells (35). BRCA1, is one of the best studied and prominent suppressors of breast cancer, mutations of which are associated with breast and/or ovarian cancer risk in addition to genetic susceptibility (36). BRCA1 exerts several effects on the DNA repair system (37).…”

Section: Pten and Brca1 Tumor Suppressors Participate In Dna Repair Imentioning

confidence: 99%

Special bioactive compounds and functional foods may exhibit neuroprotective effects in patients with dementia (Review)

et al. 2020

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Dementia is a failure of cognitive ability characterized by severe neurodegeneration in select neural systems, and Alzheimer's disease (AD) is the most common type of neurodegenerative disease. Although numerous studies have provided insights into the pathogenesis of AD, the underlying signaling and molecular pathways mediating the progressive decline of cognitive function remain poorly understood. Recent progress in molecular biology has provided an improved understanding of the importance of molecular pathogenesis of AD, and has proposed an association between DNA repair mechanisms and AD. In particular, the fundamental roles of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and breast cancer gene 1 (BRCA1) tumor suppressors have been shown to regulate the pathogenesis of neurodegeneration. Consequently, onset of neurodegenerative diseases may be deferred with the use of dietary neuroprotective agents which alter the signaling mediated by the aforementioned tumor suppressors. In a healthy neuron, homeostasis of key intracellular molecules is of great importance, and preventing neuronal apoptosis is one of the primary goals of treatments designed for dementia-associated diseases. In the present review, progress into the understanding of dietary regulation for preventing or limiting development of dementia is discussed with a focus on the modulatory roles of PTEN and BRCA1 signaling.

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Germline mutations in cancer susceptibility genes in high grade serous ovarian cancer in Serbia

Cited by 12 publications

References 43 publications

Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer

Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer

Exploring the real-world effect of the SARS-CoV-2 pandemic on the molecular diagnostics for cancer patients and high-risk individuals

Special bioactive compounds and functional foods may exhibit neuroprotective effects in patients with dementia (Review)

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