Underutilization of multigene panels among Ashkenazi Jewish patients.

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]

Are we still adjusting to multigene panel testing? An NCI-designated cancer center's 2-year experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1585-1585
Author(s):  
Chethan Ramamurthy ◽  
Mark A. Hitrik ◽  
Lyudmila DeMora ◽  
Andrea Forman ◽  
Kim Rainey ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Hereditary Cancer ◽  
Cancer Center ◽  
Genetic Tests ◽  
Detection Rates ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Disease Specific ◽  
Over Time ◽  
Multigene Panel

1585 Background: Genetic testing for hereditary cancer predisposition has rapidly changed over the past few years with the introduction of multigene panel testing. Multigene testing has evolved from disease-agnostic comprehensive (C) panels alone to include disease-specific but expanded (DSE) panels as well as guideline-based (GB) panels. We analyzed trends in utilization of genetic testing over a two-year period in one NCI-designated Cancer Center, hypothesizing that over time genetic testing usage would trend toward more disease-specific panels. Methods: We conducted a retrospective analysis of our program’s database for all germline genetic tests ordered from 9/1/2013 to 8/31/2015 (n = 619; 246 in year 1, and 373 in year 2). Tests were categorized into three groups based on specificity: GB (range: 2-12 genes tested), DSE (12-35 genes tested), and C (28-80 genes tested). The Chi-square test was used to analyze test types ordered in year 1 (9/1/2013-8/31/2014) and year 2 (9/1/2014 – 8/31/2015) and the proportions of resulting mutation types. Results: A total of 604 germline genetic tests met the inclusion criteria: 39 GB (20 year 1, 19 year 2), 171 DSE (43 year 1, 128 year 2), and 394 C (180 year 1, 214 year 2). Compared to year 1, a larger proportion of DSE tests (35% v. 18%, p < 0.001), and a smaller proportion of C tests (59% v. 74%, p < 0.001) and GB tests (5% vs. 8%, p = 0.146) were ordered. DSE panels revealed a pathogenic variant (PV) at a rate of 16% and a variant of unknown significance (VUS) at a rate of 24%. C tests revealed a PV and VUS at rates of 14% and 29%, respectively. GB tests revealed a PV and VUS at rates of 21% and 18%, respectively. No statistically significant differences in detection rates of mutation types (PV or VUS) were found between GB, DSE, or C tests. Conclusions: The rates of PV detection were not significantly different between test types, but the profile of tests ordered changed over time to favor DSE panels. Exploration of factors contributing to changing trends in genetic testing are warranted as counselors and clinicians adapt to the quickly expanding number of genes associated with hereditary cancer risks, many of them moderate-risk, and the evolving landscape of multigene panel testing.

Patterns of genetic screening for hereditary cancer syndromes: Effect of Supreme Court’s ruling invalidating single gene patent rights.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1580-1580
Author(s):  
Zhen Ni Zhou ◽  
Melissa K Frey ◽  
Dimitrios Nasioudis ◽  
Ann Carlson ◽  
Jessica Fields ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Supreme Court ◽  
Dna Sequences ◽  
Single Gene ◽  
Categorical Variables ◽  
Court Ruling ◽  
Supreme Court Ruling ◽  
Gene Testing ◽  
The Supreme Court ◽  
Multigene Panels

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]

Germline pathogenic variants in patients with pheochromocytoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 668-668
Author(s):  
Shirley A Yao ◽  
Elizabeth A Wiley ◽  
Lisa R. Susswein ◽  
Megan L. Marshall ◽  
Natalie J. Carter ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Single Gene ◽  
Molecular Data ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Testing ◽  
History Of ◽  
Testing Algorithms ◽  
Cancer Panel

668 Background: Approximately 25% of pheochromocytomas (PCC) have a hereditary basis, and germline variants in the SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, VHL, FH, RET, MEN1, and NF1 genes have been associated with a predisposition to PCC and paraganglioma (PGL). Multi-gene hereditary cancer panel testing for PCC has become increasingly more common than single-gene testing algorithms. Identification of a pathogenic or likely pathogenic variant (PV/LPV) in one of these genes has important implications for surveillance in patients and their family members. Here we describe the spectrum of PV/LPV variants identified in individuals with PCC. Methods: We performed a retrospective review of clinical and molecular data for all individuals diagnosed with PCC who underwent panel testing through BioReference Laboratories that included at least SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, VHL, FH, RET, MEN1, and NF1 between January 2016 and February 2017. Results: Seventy-nine individuals underwent testing due to a personal (n = 76) or family (n = 3) history of PCC. The positive yield was 14% (11/79). The majority of PV/LPV were in SDHB (n = 4; 36%), followed by RET (n = 2, 18%), with the remaining variants being identified in SDHA (1), SDHC (1), VHL (1), TMEM127 (1), and MAX (1). Approximately half (6/11) of those with a PV/LPV had a non-syndromic presentation of a unilateral PCC with no reported family history of PCC or PGL. The average age at tumor diagnosis was lower for probands testing positive than those without PV/LPV (34y±14 vs 44y±16). Conclusions: Our data support previous recommendations that patients with apparently sporadic, non-syndromic PCC be considered for genetic testing. Panel testing is a useful tool for identifying individuals with hereditary PCC.

Genetic Testing in Children with Epilepsy: Report of a Single-Center Experience

2020 ◽  
pp. 1-12
Author(s):  
So Lee ◽  
Natalya Karp ◽  
Eugenio Zapata-Aldana ◽  
Bekim Sadikovic ◽  
Ping Yang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Diagnostic Yield ◽  
Single Gene ◽  
Medication Management ◽  
Genetic Diagnosis ◽  
Single Center Experience ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Testing ◽  
Patients With Epilepsy

ABSTRACT: Background: Retrospective observational study to determine diagnostic yield and utility of genetic testing in children with epilepsy attending the Epilepsy Clinic at Children’s Hospital, London, Ontario, Canada. Methods: Children (birth–18 years) with epilepsy, who were seen in a 10-year period (January 1, 2008–March 31, 2018), were selected using defined inclusion criteria and by combining clinic datasets and laboratory records. Results: In total, 105 children (52.38% male and 47.61% female) with a variety of seizures were included in the analysis. Developmental delay was documented in the majority (83; 79.04%). Overall, a genetic diagnosis was established in 24 (22.85%) children. The diagnostic yield was highest for whole-exome sequencing (WES), at 35.71%. The yield from microarray was 8.33%. Yields of single-gene testing (18.60%) and targeted multigene panel testing (19.23%) were very similar. Several likely pathogenic and pathogenic variants not previously reported were identified and categorized using ACMG criteria. All diagnosed patients underwent a review of anti-seizure medication management and received counseling on natural history of their disease, possible complications, recurrence risks, and possibilities of preimplantation or prenatal genetic diagnosis. Conclusions: Our study confirms the multiple benefits of detecting a genetic etiology in children with epilepsy. Similar yields in single versus multigene testing underscore the importance of accurate clinical phenotyping. Patients with epilepsy and their caregivers in Ontario would undoubtedly benefit from repatriation of multigene panels and WES to the province.

Initial Results of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer and Lynch Syndrome

2015 ◽  
Vol 81 (10) ◽  
pp. 941-944 ◽  
Author(s):  
Dt R. Howarth ◽  
Sharon S. Lum ◽  
Pamela Esquivel ◽  
Carlos A. Garberoglio ◽  
Maheswari Senthil ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Breast And Ovarian Cancer ◽  
Variants Of Uncertain Significance ◽  
Panel Testing ◽  
Pathogenic Mutations ◽  
Uncertain Significance ◽  
Multigene Panel Testing ◽  
The Impact ◽  
Multigene Panel

Multigene panel testing for hereditary cancer risk has recently become commercially available; however, the impact of its use on patient care is undefined. We sought to evaluate results from implementation of panel testing in a multidisciplinary cancer center. We performed a retrospective review of consecutive patients undergoing genetic testing after initiating use of multigene panel testing at Loma Linda University Medical Center. From February 13 to August 25, 2014, 92 patients were referred for genetic testing based on National Comprehensive Cancer Network guidelines. Testing was completed in 90 patients. Overall, nine (10%) pathogenic mutations were identified: five BRCA1/2, and four in non-BRCA loci. Single-site testing identified one BRCA1 and one BRCA2 mutation. The remaining mutations were identified by use of panel testing for hereditary breast and ovarian cancer. There were 40 variants of uncertain significance identified in 34 patients. The use of panel testing more than doubled the identification rate of clinically significant pathogenic mutations that would have been missed with BRCA testing alone. The large number of variants of uncertain significance identified will require long-term follow-up for potential reclassification. Multigene panel testing provides additional information that may improve patient outcomes.

scholarly journals Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247363
Author(s):  
Renata Lazari Sandoval ◽  
Ana Carolina Rathsam Leite ◽  
Daniel Meirelles Barbalho ◽  
Daniele Xavier Assad ◽  
Romualdo Barroso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Multiple Primary Cancers ◽  
Panel Testing ◽  
History Of ◽  
Multigene Panel Testing ◽  
Positive Results ◽  
Actionable Variants ◽  
Multigene Panel

Brazil is the largest country in South America and the most genetically heterogeneous. The aim of the present study was to determine the prevalence of germline pathogenic variants (PVs) in Brazilian patients with breast cancer (BC) who underwent genetic counseling and genetic testing at a tertiary Oncology Center. We performed a retrospective analysis of the medical records of Brazilian patients with BC referred to genetic counseling and genetic testing between August 2017 and August 2019. A total of 224 unrelated patients were included in this study. Premenopausal women represented 68.7% of the cohort. The median age at BC diagnosis was 45 years. Multigene panel testing was performed in 219 patients, five patients performed single gene analysis or family variant testing. Forty-eight germline PVs distributed among 13 genes were detected in 20.5% of the patients (46/224). Eighty-five percent of the patients (91/224) fulfilled NCCN hereditary BC testing criteria. Among these patients, 23.5% harbored PVs (45/191). In the group of patients that did not meet NCCN criteria, PV detection rate was 3% (1/33). A total of 61% of the patients (28/46) harbored a PV in a high-penetrance BC gene: 19 (8.5%) BRCA1/2, 8 (3.5%) TP53, 1 (0.5%) PALB2. Moderate penetrance genes (ATM, CHEK2) represented 15.2% (7/46) of the positive results. PVs detection was statistically associated (p<0.05) with BC diagnosis before age 45, high-grade tumors, bilateral BC, history of multiple primary cancers, and family history of pancreatic cancer. According to the current hereditary cancer guidelines, 17.4% (39/224) of the patients had actionable variants. Nine percent of the patients (20/224) had actionable variants in non-BRCA genes, it represented 43.5% of the positive results and 51.2% of the actionable variants. Considering the observed prevalence of PVs in actionable genes beyond BRCA1/2 (9%, 20/224), multigene panel testing may offer an effective first-tier diagnostic approach in this population.

scholarly journals Implications of Multigene Panel Testing on Psychosocial Outcomes: A Comparison of Patients With Pancreatic and Breast or Ovarian Cancer

2021 ◽  
pp. 235-244
Author(s):  
Cathryn Koptiuch ◽  
Whitney F. Espinel ◽  
Wendy K. Kohlmann ◽  
Jingsong Zhao ◽  
Kimberly A. Kaphingst
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Genetic Test ◽  
Emotional Reactions ◽  
Test Results ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Genetic Test Results ◽  
Multigene Panel Testing ◽  
Multigene Panel

PURPOSE National Comprehensive Cancer Network guidelines for germline genetic testing have included pancreatic cancer in the context of additional family cancer history for many years but this was not recommended for patients with pancreatic ductal adenocarcinoma (PDAC) independent of a family history until 2019. This hypothesis-generating study reports the results from multigene panel testing for PDAC patients at an academic medical center. PATIENTS AND METHODS This prospective longitudinal feasibility study examined responses to genetic counseling and multigene panel testing among PDAC and breast or ovarian cancer (BrOv) patients between October 2016 and November 2017. Pre- and post-test surveys assessed perceptions of genetic risk and testing, recall, comprehension, and emotional reactions to results using open-ended and closed-ended items. RESULTS Forty-six BrOv and 33 PDAC patients were enrolled, and 44 BrOv and 31 PDAC participants underwent genetic testing. Seven pathogenic variants were identified in six BrOv participants (13.6%), and three pathogenic variants were identified in three PDAC participants (9.7%). The majority of both cohorts expressed similar attitudes about the importance of genetic testing for their personal and family medical management and expressed accurate understanding of implications of their results. Although sample size was small, there were no significant differences between the BrOv and PDAC cohorts for positive or negative emotions. CONCLUSION This study points to high rates of positive emotions and low rates of negative emotions following genetic test results, suggesting that the emotional reactions to genetic test results are similar for patients with BrOv and PDAC, despite poor prognosis with PDAC diagnoses. Because of the unique needs of the PDAC population following diagnosis, a multidisciplinary approach to germline genetic testing following diagnosis may result in best patient and family member outcomes.

scholarly journals Increased use of genetic health care in Iceland 2012-2017

2022 ◽  
Vol 108 (01) ◽  
pp. 11-16
Author(s):  
Hákon Björn Högnason ◽  
◽  
Vigdís Fjóla Stefánsdóttir ◽  
Eirný Þöll Þórólfsdóttir ◽  
Jón Jóhannes Jónsson ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Counselling ◽  
Single Gene ◽  
Gene Panel ◽  
Whole Genome ◽  
Panel Testing ◽  
Gene Testing ◽  
Time Period ◽  
Whole Exome ◽  
Gene Panel Testing

INTRODUCTION: A genetic counselling unit at Landspitali hospital (LSH) was established in 2006. Meanwhile, genetic testing has become an integral part of general health care. In this article we detail the outcome of genetic testing at the Department of Genetic and Molecular Medicine (DGM) at Landspitali over a five year period (2012-2017). Factors that were analyzed for the time period were: Number of patients, reason for referral, reason for genetic testing without genetic counselling and yield (proportion of positive tests) of genetic testing. METHODS: Data was analysed from two medical record databases, Shire and Saga, used by the DGM in the time period. RESULTS: The number of individuals coming for genetic counselling increased every year over the time period. Reasons for referral were cancer-related in two-thirds of cases. Other reasons for referral included various other familial disorders. Most common were autosomal dominant disorders like myotonic dystrophy, hypertrophic cardiomyopathy and autosomal recessive disorders like spinal muscular atrophy (SMA) and GM1-gangliosidosis. Most common reasons for genetic testing outside of the LSH GC unit was because of managable diseases like hemochromatosis and F5/Prothrombin-related thrombophilia. Yield of genetic testing was assessed for a) known mutation testing / carrier testing, b) single gene testing, c) gene panel testing and d) whole genome and whole exome sequencing. Known mutation testing was positive in 33% of cases and single gene testing in 46% of cases. The yield of gene panel testing for cancer was found to be lower (20%) than gene panel testing for other disorders (40%). The yield of whole exome and whole genome sequencing was 46%.

BRCA1/2 and multigene panel testing among metastatic breast, pancreas, prostate, and ovarian cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13160-e13160
Author(s):  
Meghna S. Trivedi ◽  
VanAnh L Vo ◽  
Tarsha Jones ◽  
Thomas Silverman ◽  
Wendy Chung ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Patients ◽  
Metastatic Cancer ◽  
Genetic Counselor ◽  
Private Insurance ◽  
Metastatic Breast ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

e13160 Background: Given the availability of targeted therapies such as PARP inhibitors, patients with metastatic breast, pancreas, prostate, and ovarian cancer are recommended to have germline genetic testing for hereditary cancer syndromes. Completion of genetic testing among this population is understudied. Methods: We performed a retrospective study of 548 patients with stage 4 breast, pancreas, prostate, and ovarian cancer at diagnosis from January 2013-December 2017 identified in the New York Presbyterian Hospital Tumor Registry at Columbia University Irving Medical Center. Data on socio-demographics, clinical factors, and genetic testing completion and results were collected from the medical record. We conducted descriptive statistics. Results: Our study population had a median age of 66 years (range, 23-97) at diagnosis; 61% female; 50% non-Hispanic white/22% Hispanic/15% non-Hispanic black/5% Asian/7% other; 33% private insurance/16% Medicaid/44% Medicare/7% unknown insurance. Primary cancer was 24% breast, 8% ovary, 61% pancreas, and 7% prostate. Only 38 patients were seen by a genetic counselor (7%) and only 50 (9%) had genetic testing performed. Among those who underwent germline testing, 92% had multigene panel testing (median number of genes tested 13.5, range 2-74). Pathogenic variants were detected in 6 patients (12%), of which 4 had a BRCA1/2 mutation, and 26% had a variant of uncertain significance (VUS). Conclusions: We found that only a small percentage of metastatic breast, pancreas, prostate, and ovarian cancer patients underwent genetic testing. Further research is necessary to identify the barriers to genetic testing uptake in metastatic cancer patients. BRCA1/2 and multigene panel testing has important implications in this patient population not only for treatment decisions, but also to increase cascade testing in unaffected family members who may be at risk for malignancy in the future.

Sign in / Sign up

Export Citation Format

Share Document