Evaluation of <i>BRCA1/2</i> gene mutations in patients with high-risk breast and/or ovarian cancer in Turkey

Ödemiş, Demet Akdeniz; Çelik, Betül; Erciyas, Seda Kılıç; Erdoğan, Özge; Tunçer, Şeref Buğra; Gultaslar, Busra Kurt; Ghafour, Arash Adamnejad; Saip, Pınar; Yazıcı, Hülya

doi:10.1515/tjb-2021-0209

Cited by 3 publications

(1 citation statement)

References 22 publications

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“…Furthermore, noncoding mutations in introns also affect splicing and thus the generated proteins ( Jung et al 2021 ). Not only that, silent mutations (which cause no change in an amino acid sequence) and which were thought to be mostly harmless, were also discovered to play significant roles in cancer prognosis ( Gutman et al 2021 , Odemis et al 2022 ). As a result, most of which was thought to be correct with regards to mutations in the past century is currently being re-evaluated.…”

Section: Methodsmentioning

confidence: 99%

Mutate and observe: utilizing deep neural networks to investigate the impact of mutations on translation initiation

et al. 2023

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Motivation The primary regulatory step for protein synthesis is translation initiation, which makes it one of the fundamental steps in the central dogma of molecular biology. In recent years, a number of approaches relying on deep neural networks (DNNs) have demonstrated superb results for predicting translation initiation sites. These state-of-the art results indicate that DNNs are indeed capable of learning complex features that are relevant to the process of translation. Unfortunately, most of those research efforts that employ DNNs only provide shallow insights into the decision-making processes of the trained models and lack highly sought-after novel biologically relevant observations. Results By improving upon the state-of-the-art DNNs and large-scale human genomic datasets in the area of translation initiation, we propose an innovative computational methodology to get neural networks to explain what was learned from data. Our methodology, which relies on in silico point mutations, reveals that DNNs trained for translation initiation site detection correctly identify well-established biological signals relevant to translation, including (1) the importance of the Kozak sequence, (2) the damaging consequences of ATG mutations in the 5’ untranslated region (UTR), (3) the detrimental effect of premature stop codons in the coding region, and (4) the relative insignificance of cytosine mutations for translation. Furthermore, we delve deeper into the Beta-globin gene and investigate various mutations that lead to the Beta thalassemia disorder. Finally, we conclude our work by laying out a number of novel observations regarding mutations and translation initiation. Availability For data, models, and code, visit github.com/utkuozbulak/mutate-and-observe Supplementary information Supplementary data are available at Bioinformatics online.

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Section: Methodsmentioning

confidence: 99%

Mutate and observe: utilizing deep neural networks to investigate the impact of mutations on translation initiation

et al. 2023

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Factors associated with psychological distress during genetic counseling in high-risk women with breast cancer in Turkey

Anuk,

Tuncer,

Özkan

et al. 2024

Support Care Cancer

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Purpose This study aims to shed light on the rather neglected area of research of psychological distress in women facing genetic counselling in Turkey, where few institutions providing such counselling exist. Methods 105 breast cancer patients presenting for genetic testing completed a sociodemographic and clinical questionnaire as well as validated structured questionnaires including the Beck Depression Inventory (BDI), the State–Trait Anxiety Inventory (STAI-S/T) and the Health Motivation Sub-dimension of Champion’s Health Belief Model Scale. Results 69.5% of the participants had lost a family member from cancer; 80% said the term “cancer” elicited negative thoughts (e.g., death, fear, and incurable disease). 62.9% and 37.1% attributed cancer to stress or sorrow, and genetic susceptibility, respectively. There was a negative association between health motivation and BDI scores (r:-0.433, p < 0.001). Married individuals had higher BDI and STAI-S scores (p = 0.001, p = 0.01 respectively), as well as lower STAI-T scores (p = 0.006). BDI, STAI-S and STAI-T scores were higher in those refusing genetic testing (p < 0.001, p < 0.001, p = 0.003 respectively) and those with metastases (p = 0.03, p = 0.01, p = 0.03 respectively). Furthermore, individuals with low health motivation were more likely to exhibit high BDI scores (p < 0.001) and low STAI-T scores (p = 0.02). Conclusion Common perceptions and beliefs about cancer and genetic testing during genetic counselling were found to have a negative impact on distress in high-risk women with breast cancer. The negative relationship between psychological distress and health motivation may reduce patients' compliance with genetic counselling recommendations. A comprehensive psychological evaluation should be considered as an important part of genetic counselling.

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Molecular profiling of BRCA1 and BRCA2 genes in Turkish patients with early-onset breast cancer

Karakaya,

Kocaaga

2023

Egypt J Med Hum Genet

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Background Early-onset breast cancer (EOBC) is a specific condition that affects women under the age of 45. BRCA pathogenic/likely pathogenic (P/LP) germline variants have been demonstrated to be harbored in a subgroup of EOBC individuals, and BRCA-positive genetic result offers an option to ensure more specified therapeutic implications. Establishing comprehensive BRCA1/2 genetic testing, including both the detection of small-scale mutations and large genomic rearrangements (LGRs), is needed for risk assessment and clinical management. In this study, we described a Turkish EOBC cohort along with their clinico-pathological characteristics and BRCA1/2 mutational profiles. A total of 67 unrelated patients were enrolled. Both next-generation sequencing (NGS)-based gene panel and multiplex ligation-dependent probe amplification (MLPA) were performed for BRCA1/2 variant identification. Patients' family medical history and hormone receptor status of the tumors were also recorded. Results 14 (20.90%) patients were found to carry BRCA P/LP germline variants. (Nine were BRCA2-positive, and five were BRCA1-positive.) Two novel BRCA2 variants were detected. No significant differences were found between BRCA-positive vs. BRCA-negative or BRCA1-positive vs. BRCA2-positive for hormonal status and family history. Conclusions BRCA1/2 genes represent a predominant part of the genetic landscape of EOBC. Our results expand the spectrum of BRCA1/2 variants and provide knowledge of the BRCA1/2 variant prevalence in our cohort.

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Evaluation of BRCA1/2 gene mutations in patients with high-risk breast and/or ovarian cancer in Turkey

Cited by 3 publications

References 22 publications

Mutate and observe: utilizing deep neural networks to investigate the impact of mutations on translation initiation

Mutate and observe: utilizing deep neural networks to investigate the impact of mutations on translation initiation

Factors associated with psychological distress during genetic counseling in high-risk women with breast cancer in Turkey

Molecular profiling of BRCA1 and BRCA2 genes in Turkish patients with early-onset breast cancer

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