Variants of Uncertain Significance in<i>BRCA1</i>and<i>BRCA2</i>assessment of in silico analysis and a proposal for communication in genetic counselling

Moghadasi, Setareh; Hofland, Nandy; Wouts, Joyce N; Hogervorst, Frans B.L.; Wijnen, Juul T.; Vreeswijk, Maaike P.G.; Asperen, Christi J. van

doi:10.1136/jmedgenet-2012-100961

Cited by 20 publications

(15 citation statements)

References 24 publications

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“…Multiple strategies are often combined and required to determine if a VUS is pathogenic or benign (Eggington et al, 2014;Millot et al, 2012;Moghadasi et al, 2013;Radice, De Summa, Caleca, & Tommasi, 2011;Rehm et al, 2013;Sijmons, Greenblatt, & Genuardi, 2013). Most laboratories use a variety of methods to reclassify a variant (see Figure 2).…”

Section: Reclassification Strategiesmentioning

confidence: 99%

Management of Patients With a Genetic Variant of Unknown Significance

Mahon

2015

ONF

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Accurate risk assessment of developing cancer often includes genetic testing for germline mutations, which has clinical and treatment implications for the patient and his or her family members. When a mutation is detected, aggressive measures for cancer prevention and detection are often implemented. Depending on the gene or genes tested, a variable percentage of patients will receive a test report stating that a variant of unknown significance (VUS) has been detected. This means that a change in the genetic sequence has occurred, but whether the change is associated with an increased risk of cancer or another disease is unclear or unknown. The results are confusing and noninformative. Oncology nurses will undoubtedly encounter patients with a VUS; consequently, they need to understand the controversies and ambiguities that surround these test results. Resources that may be offered by healthcare providers and aid in patient understanding of VUS results are available (see Figure 1).

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Section: Reclassification Strategiesmentioning

confidence: 99%

Management of Patients With a Genetic Variant of Unknown Significance

Mahon

2015

ONF

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“…Therefore, it is not yet possible to report VUS using a universally accepted reference. Using multiple references from international networks to collect and interpret VUS data including clinical, functional, pathological, and in silico analyses may provide a way to share comprehensive BRCA1/2 information [25]. For now, using a single reference for interpreting VUS data should be avoided.…”

Section: Discussionmentioning

confidence: 99%

Next-generation sequencing of BRCA1/2 in breast cancer patients: potential effects on clinical decision-making using rapid, high-accuracy genetic results

Park

Kim

et al. 2017

Ann Surg Treat Res

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PurposeWe evaluated the clinical role of rapid next-generation sequencing (NGS) for identifying BRCA1/2 mutations compared to traditional Sanger sequencing.MethodsTwenty-four paired samples from 12 patients were analyzed in this prospective study to compare the performance of NGS to the Sanger method. Both NGS and Sanger sequencing were performed in 2 different laboratories using blood samples from patients with breast cancer. We then analyzed the accuracy of NGS in terms of variant calling and determining concordance rates of BRCA1/2 mutation detection.ResultsThe overall concordance rate of BRCA1/2 mutation identification was 100%. Variants of unknown significance (VUS) were reported in two cases of BRCA1 and 3 cases of BRCA2 after Sanger sequencing, whereas NGS reported only 1 case of BRCA1 VUS, likely due to differences in reference databases used for mutation identification. The median turnaround time of Sanger sequencing was 22 days (range, 14–26 days), while the median time of NGS was only 6 days (range, 3–21 days).ConclusionNGS yielded comparably accurate results to Sanger sequencing and in a much shorter time with respect to BRCA1/2 mutation identification. The shorter turnaround time and higher accuracy of NGS may help clinicians make more timely and informed decisions regarding surgery or neoadjuvant chemotherapy in patients with breast cancer.

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“…In a disorder like breast cancer, the frequency of VUS fi ndings in genes like BRCA1 and BRCA2 is around 15 % of results [ 15 ].…”

Section: Traditional Approachmentioning

confidence: 99%

Direct-to-Consumer DNA Genetic and Genomic Testing

Trent

2015

Movement Disorder Genetics

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Direct-to-consumer (DTC) DNA genetic and genomic testing refers to the provision of DNA testing services by a laboratory directly to the public. The DTC industry emerged in the early 2000s and offered a range of DNA testing options for medical and other applications. The DTC approach is possible because DNA can be transported by mail, and the expanding role of the Internet in everyday life allows products to be advertised widely. The media and some in the scientifi c community helped the industry by highlighting new discoveries in genetic knowledge which were research-in-progress although packaged as having immediate benefi ts to health and well-being. The DTC industry has undergone a number of changes and is at a defi ning moment as regulators and the courts are asking questions about the product for sale. The model of care exemplifi ed by the DTC approach is attractive and likely to grow although the role of a medical practitioner in DTC DNA testing remains uncertain.

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Variants of Uncertain Significance inBRCA1andBRCA2assessment of in silico analysis and a proposal for communication in genetic counselling

Cited by 20 publications

References 24 publications

Management of Patients With a Genetic Variant of Unknown Significance

Management of Patients With a Genetic Variant of Unknown Significance

Next-generation sequencing of BRCA1/2 in breast cancer patients: potential effects on clinical decision-making using rapid, high-accuracy genetic results

Direct-to-Consumer DNA Genetic and Genomic Testing

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