Customized multigene panels in epilepsy: the best things come in small packages

1580 Background: In 6/2013 the Supreme Court ruled that isolated DNA sequences found in nature could not be patented, resulting in rapid uptake of multigene panels. We sought to explore trends in genetic testing since this ruling. Methods: Results of all patients undergoing genetic testing and counseling at a single institution between 7/1/13 and 12/31/16 were reviewed. Associations between categorical variables were evaluated by chi-square tests or Fisher's exact tests as appropriate for category size. Results: 1663 patients underwent genetic testing over the study period. The median age was 49 years (range 18-86). Use of multigene panels versus targeted gene testing increased significantly in the years following the Supreme Court ruling (Table 1, P<0.001). While the percentage of patients found to have pathogenic mutations remained stable over the study period (9%), detection of variants of uncertain significance (VUS) increased significantly (Table 1, P<0.001). In 2013 BRCA1/2 mutations accounted for 91% of identified mutations; however this number decreased over time (2014-83%, 2015-70%, 2016-58%, P=0.01). Use of multigene panels detected 71% of mutations in non- BRCA1/2 genes such as CHEK(19), APC(44), MSH6(1), P53(1), and PTEN(1). Patients with a personal history of breast and/or ovarian cancer were more likely to have targeted testing than patients with other cancer types (590, 66% vs. 9, 33%, P=0.001). Conclusions: The uptake of multigene panels has increased since the 2013 Supreme Court ruling. While this technology allowed for the identification of many cancer-related genes that would be missed on targeted BRCA1/2 testing, it also resulted in a significantly increased detection of VUS, a finding with unknown clinical implications. [Table: see text]

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Outcomes of retesting BRCA negative patients using multigene panels

Familial Cancer ◽

10.1007/s10689-016-9956-7 ◽

2016 ◽

Vol 16 (3) ◽

pp. 319-328 ◽

Cited By ~ 5

Author(s):

Siddhartha Yadav ◽

Ashley Reeves ◽

Sarah Campian ◽

Amy Paine ◽

Dana Zakalik

Keyword(s):

Multigene Panels ◽

Brca Negative

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Improving performance of multigene panels for genomic analysis of cancer predisposition

Genetics in Medicine ◽

10.1038/gim.2015.212 ◽

2016 ◽

Vol 18 (10) ◽

pp. 974-981 ◽

Cited By ~ 42

Author(s):

Brian H. Shirts ◽

Silvia Casadei ◽

Angela L. Jacobson ◽

Ming K. Lee ◽

Suleyman Gulsuner ◽

...

Keyword(s):

Genomic Analysis ◽

Cancer Predisposition ◽

Multigene Panels

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COLUMNS

Asia-Pacific Biotech News ◽

10.1142/s0219030318000769 ◽

2018 ◽

Vol 22 (11) ◽

pp. 16-24 ◽

Cited By ~ 2

Keyword(s):

Next Generation Sequencing ◽

Next Generation ◽

Multigene Panels ◽

Generation Sequencing

Asian oncologists’ perception in adopting next-generation sequencing multigene panels. Time to get serious.

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Germline mutational spectrum of Brazilian HBOC patients tested with hereditary cancer multigene panels.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e13113 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e13113-e13113

Author(s):

Barbara Alemar ◽

Cristina Netto ◽

Camila Bittar ◽

Osvaldo Artigalas ◽

Cleandra Gregorio ◽

...

Keyword(s):

Hereditary Cancer ◽

Mutational Spectrum ◽

Multigene Panels

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Underutilization of multigene panels among Ashkenazi Jewish patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1533 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1533-1533

Author(s):

Jessica Fields ◽

Dimitrios Nasioudis ◽

Zhen Ni Zhou ◽

Ann Carlson ◽

Melissa Kristen Frey ◽

...

Keyword(s):

Genetic Testing ◽

Single Gene ◽

Cancer Center ◽

Ashkenazi Jewish ◽

Panel Testing ◽

Gene Testing ◽

Multigene Panels ◽

Multigene Panel Testing ◽

Genetic Assessment ◽

Multigene Panel

1533 Background: Approximately one in forty Ashkenazi Jewish (AJ) individuals carry a BRCA1/2 mutation and genetic screening in this population has largely focused on these two genes. With the recent rapid uptake of multigene panel testing for cancer genetic assessment, we sought to explore multigene panels in our cohort which is comprised of AJ and non-AJ patients. Methods: The results of all patients with known ancestry who underwent genetic testing and counseling at the hereditary breast and ovarian cancer center at a single institution between 7/1/2013-12/31/2016 were reviewed. Results: One thousand six hundred and fifty patients with known ancestry underwent genetic testing over the study period, including 681 AJ patients. The median age was 49 (range 20-86). AJ patients were more likely to undergo targeted testing than non-AJ patients (74% vs. 61 %, P<0.001). The use of multigene panels in AJ patients increased over time (2013 – 3.2%, 2014 – 18.7%, 2015 – 27.4%, 2016 – 48.4%, P<0.001). Mutations were more common in AJ patients (75, 11% vs. 66, 7%, P=0.003). Variants of uncertain significance (VUS) were less common in AJ patients (40, 6% vs. 124, 13%, P<0.001), even when excluding patients with single gene testing (32, 19% vs. 98, 27%, P=0.05). Among all patients, mutations in BRCA1/2 were most common (75%). The majority (69%) of non- BRCA1/2 mutations were identified on multigene panels. Rates of mutations in non- BRCA1/2 genes were the same among AJ and non-AJ patients (16, 21% vs. 20, 30%, P=0.3, Table 1). Conclusions: AJ patients have equivalent rates of non- BRCA1/2 mutations and on multigene panels have lower rates of VUS compared to non-AJ patients. However, the majority of AJ patients underwent targeted gene testing. These findings suggest consideration of a change in paradigm for genetic assessment of AJ patients with a focus on BRCA and non- BRCAassociated cancer genes through multigene panel testing. [Table: see text]

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