Clinical Contribution of Next-Generation Sequencing Multigene Panel Testing for BRCA Negative High-Risk Patients With Breast Cancer

Solmaz, Aslı Ece; Yenıay, Levent; Gökmen, Erhan; Zekioğlu, Osman; Haydaroğlu, Ayfer; Bilgen, Işıl Günhan; Özkınay, Ferda; Önay, Hüseyin

doi:10.1016/j.clbc.2021.04.002

Cited by 10 publications

(6 citation statements)

References 42 publications

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“…Solmaz et al. (2021) analyzed 18 genes in 188 BRCA ‐negative Turkish patients and identified P/LP variants in 11.1% and VUS variants in 15.9% of the patients. The reason for these different results may be the different gene contents in the panels used and patient populations of various origins.…”

Section: Discussionmentioning

confidence: 99%

“…Several NGS studies have reported breast cancer cases that involve non‐ BRCA genes (Lang et al., 2020; Schubert et al., 2019; Solmaz et al., 2021; Zanti et al., 2020), but to date, there is limited data on the variation spectrum of non‐ BRCA genes in Turkish individuals at risk for hereditary breast cancer. Therefore, in this study, it was aimed to identify genetic variations in 34 non‐ BRCA genes, which have key roles in various signaling pathways in the cell and are proven to be or might be associated with breast cancer, and explain their potential roles in the pathogenesis of the disease, suggests potential treatment possibilities, and identify other family members at risk.…”

Section: Introductionmentioning

confidence: 99%

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The role of next‐generation sequencing in the examination of signaling genes in Brca1/2‐negative breast cancer cases

Çine

Ugurtas

Gökbayrak

et al. 2022

Annals of Human Genetics

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Introduction: Breast cancer is the most prevalent malignancy in women worldwide. Although pathogenic variants in the BRCA1/2 genes are responsible for the majority of hereditary breast cancer cases, a substantial proportion of patients are negative for pathogenic variations in these genes. In cancers, the signal transduction pathways of the cell are usually affected first. Therefore, this study aimed to detect and classified genetic variations in non-BRCA signaling genes and investigate the underlying genetic causes of susceptibility to breast cancer. Methods: Ninety-six patients without pathogenic variants in the BRCA1/2 genes who met the inclusion criteria were enrolled in the study, and 34 genes were analyzed using next-generation sequencing (NGS) for genetic analysis.Results: Based on the ClinVar database or American College of Medical Genetics criteria, a total of 55 variants of 16 genes were detected in 43 (44.8%) of the 96 patients included in the study. The pathogenic variants were found in the TP53, CHEK2, and RET genes, whereas the likely pathogenic variants were found in the FGFR1, FGFR3, EGFR, and NOTCH1 genes. Conclusion:The examination of signaling genes in patients who met the established criteria for hereditary breast cancer but were negative for BRCA1/2 pathogenic variants provided additional information for approximately 8% of the families. The results of the present study suggest that NGS is a powerful tool for investigating the underlying genetic causes of occurrence and progression of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of next‐generation sequencing in the examination of signaling genes in Brca1/2‐negative breast cancer cases

Çine

Ugurtas

Gökbayrak

et al. 2022

Annals of Human Genetics

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“…Other genes carry a differential risk depending on the BC immunophenotype: BARD1, RAD51C, and RAD51D mutations are associated with a higher risk of ER-negative BCs, including TNBCs, whereas ATM and CHK2 mutations are associated with a higher risk of ER+ BC. Although germline mutations in BRIP1, MUTYH, or OGG have been reported, their association with BC risk remains unclear [4][5][6]).…”

Section: Germline Mutations Of Additional Dna Damage Response (Ddr)-associated Genesmentioning

confidence: 99%

Recent Advances in Enhancing the Therapeutic Index of PARP Inhibitors in Breast Cancer

Franchet

Hoffmann

2021

Cancers

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As poly-(ADP)-ribose polymerase (PARP) inhibition is synthetic lethal with the deficiency of DNA double-strand (DSB) break repair by homologous recombination (HR), PARP inhibitors (PARPi) are currently used to treat breast cancers with mutated BRCA1/2 HR factors. Unfortunately, the increasingly high rate of PARPi resistance in clinical practice has dented initial hopes. Multiple resistance mechanisms and acquired vulnerabilities revealed in vitro might explain this setback. We describe the mechanisms and vulnerabilities involved, including newly identified modes of regulation of DSB repair that are now being tested in large cohorts of patients and discuss how they could lead to novel treatment strategies to improve the therapeutic index of PARPi.

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“…The present study involved around 100 unaffected individuals, selected only based on their familiar cancer history in the absence of a positive familiar member. Furthermore, we focused on the potential impact of a Next Generation Sequencing (NGS)-based multi-gene panel of 27 genes, including BRCA1/2 genes, with the aim to understand whether expanding the analysis to a larger panel of genes may result into a percentage of healthy subjects with cancer-predisposing gene variants higher than that reported in previous studies [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The Crucial Role of Hereditary Cancer Panel Testing in Unaffected Individuals with a Strong Family History of Cancer: A Retrospective Study of a Cohort of 103 Healthy Subjects

Pilenzi,

Anaclerio,

Dell’Elice

et al. 2024

Preprint

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Hereditary cancer syndromes caused by germline mutations account for 5-10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network’s (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status.

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Clinical Contribution of Next-Generation Sequencing Multigene Panel Testing for BRCA Negative High-Risk Patients With Breast Cancer

Cited by 10 publications

References 42 publications

The role of next‐generation sequencing in the examination of signaling genes in Brca1/2‐negative breast cancer cases

The role of next‐generation sequencing in the examination of signaling genes in Brca1/2‐negative breast cancer cases

Recent Advances in Enhancing the Therapeutic Index of PARP Inhibitors in Breast Cancer

The Crucial Role of Hereditary Cancer Panel Testing in Unaffected Individuals with a Strong Family History of Cancer: A Retrospective Study of a Cohort of 103 Healthy Subjects

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