New challenges for BRCA testing: a view from the diagnostic laboratory

Wallace, Andrew

doi:10.1038/ejhg.2016.94

Cited by 77 publications

(58 citation statements)

References 69 publications

(78 reference statements)

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“…At present, the majority of test centers in China use a second‐generationhigh‐throughput sequencing technique to detect BRCA mutations and to classify mutations into one of the following categories: pathogenic mutation, suspected pathogenic mutation, mutation of unknown clinical significance, suspected benign mutation, and benign mutation . This approach is cost‐efficient but does not detect structural variations and variations in gene regulatory regions of the BRCA gene . Furthermore, due to the lack of genetic experts in the country, interpretation of BRCA test results can be challenging .…”

Section: Discussionmentioning

confidence: 99%

Real‐world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau

et al. 2019

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Background: Olaparib has been approved as an active and maintenance therapy for patients with platinum-sensitive, BRCA-mutated high-grade serous ovarian cancer (SOC). However, the efficacy and safety data is lack among Chinese ovarian cancer patients.Aim: This real-world study aimed to evaluate the effectiveness and safety profile of olaparib in patients from mainland China, where olaparib is currently unavailable. Methods and results: This single-center, observational study included 65 patients with pathologically confirmed advanced serous ovarian cancer from Kiang Wu Hospital in Macau between December 2015 and September 2017. Progression-free survival (PFS) and other endpoints (treatment response, disease progression, and adverse events) were evaluated. PFS was estimated using the Kaplan-Meier method.The median treatment duration was 4 months (range, 1-15). The median PFS for the overall population was 4.2 months (95% CI 2.7-5.2), while those for patients with wild-type BRCA1/2 and BRCA1/2 mutations were 3.1 months (95% CI 1.3-4.6) and 5.3 months (95% CI 2.8-7.1), respectively. The median PFS tended to be longer for patients on maintenance therapy (between 9.0 months [95% CI 1.4-17.5] and 10.0 months [95% CI 2.5-18.1]) than for those on active therapy (between 3.1 months [95% CI 2.1-3.8] and 3.0 months [95% CI 1.4-4.5]). Most patients (87.0%) experienced low-grade adverse events; the most common of which were fatigue (49.0%) and nausea (35.0%). Conclusion: Our findings demonstrate clinical benefit of olaparib to mainlandChinese patients with high-grade SOC, particularly for patients with BRCA mutations and who require maintenance therapy.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Discussionmentioning

confidence: 99%

Real‐world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau

et al. 2019

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“…Since gBRCA testing is nowadays performed by Next Generation Sequencing (NGS) [18] our Unit has never had any particular programming issues related to availability of samples to program the sequencing run. We were always able to organize sequencing run using any available Illumina sequencing flow cell format (NGS platform used in our Unit).…”

Section: Introductionmentioning

confidence: 99%

BRCA testing in a genomic diagnostics referral center during the COVID-19 pandemic

et al. 2020

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The first person-to-person transmission of the 2019-novel coronavirus in Italy on 21 February 2020 led to an infection chain that represents one of the largest known COVID-19 outbreaks outside Asia. Hospitals have been forced to reorganized their units in response to prepare for an unforeseen healthcare emergency. In this context, our laboratory (Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS) re-modulated its priorities by temporarily interrupting most of the molecular tests guaranteeing only those considered "urgent" and not postponable. In particular, this paper details changes regarding the execution of germline BRCA (gBRCA ) testing in our laboratory. A substantial reduction in gBRCA testing (about 60%) compared to the first 2 months of the current year was registered, but the requests have not been reset. The requesting physicians were mainly gynaecologists and oncologists. These evidences further emphasize the new era of gBRCA testing in the management of cancer patients and confirms definitively the integration of gBRCA testing/ Next Generation Sequencing (NGS) into clinical oncology. Finally, a re-organization of gBRCA testing in our Unit, mainly related to delayed and reduced arrival of tests was necessary, ensuring, however, a high-quality standard and reliability, mandatory for gBRCA testing in a clinical setting.

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“…A successful genetic diagnosis relies on the correct interpretation of genetic results. However, BRCA1/2 genetic testing in clinical laboratories commonly identifies variants of unknown significance (VUS) from which sequencing information alone is not sufficient for variant clinical classification, failing to provide a clear genetic diagnosis (Eccles et al, ; Wallace, ). One group of VUS is represented by variants that have the potential to alter the messenger RNA (mRNA) splicing process.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of semi‐quantitative analysis of splicing alterations for the clinical interpretation of variants inBRCA1andBRCA2genes

Montalban¹,

Bonache²,

Moles‐Fernández³

et al. 2019

Human Mutation

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BRCA1 and BRCA2 (BRCA1/2) genetic variants that disrupt messenger RNA splicing are commonly associated with increased risks of developing breast/ovarian cancer.The majority of splicing studies published to date rely on qualitative methodologies (i.e., Sanger sequencing), but it is necessary to incorporate semi-quantitative or quantitative approaches to accurately interpret the clinical significance of spliceogenic variants. Here, we characterize the splicing impact of 31 BRCA1/2 variants using semi-quantitative capillary electrophoresis of fluorescent amplicons (CE), Sanger sequencing and allele-specific assays. A total of 14 variants were found to disrupt splicing. Allelic-specific assays could be performed for BRCA1 c.302−1G>A and BRCA2 c.

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New challenges for BRCA testing: a view from the diagnostic laboratory

Cited by 77 publications

References 69 publications

Real‐world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau

Real‐world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau

BRCA testing in a genomic diagnostics referral center during the COVID-19 pandemic

Incorporation of semi‐quantitative analysis of splicing alterations for the clinical interpretation of variants inBRCA1andBRCA2genes

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