Genotype-phenotype correlations among TP53 carriers: Literature review and analysis of probands undergoing multi-gene panel testing and single-gene 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%.

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Benefits and safety of multigene panel testing in patients at risk for hereditary breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.16 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 16-16

Author(s):

Nimmi S. Kapoor ◽

Lisa D. Curcio ◽

Carlee A. Blakemore ◽

Amy K. Bremner ◽

Rachel E. McFarland ◽

...

Keyword(s):

Breast Cancer ◽

At Risk ◽

Genetic Testing ◽

Hereditary Breast Cancer ◽

Diagnostic Yield ◽

Gene Panel ◽

Panel Testing ◽

Gene Testing ◽

Gene Panel Testing ◽

Patients At Risk

16 Background: Recently introduced multi-gene panel testing including BRCA1 and BRCA2 genes (BRCA1/2) for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study is to evaluate rates of pathogenic BRCA1/2mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multi-gene testing. Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2testing only (limited group, n = 629) to those who underwent multi-gene testing with 5-43 cancer-related genes (panel group, n = 337). Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0% vs 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5% vs 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9% (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. Conclusions: Multi-gene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly due to non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from upfront, more efficient, multi-gene panel testing.

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The Advent of Gene Panel Testing: Has It Changed the Outcome of Mutation Detection Gene Testing in a Cardiac Genetics Clinic?

Heart Lung and Circulation ◽

10.1016/j.hlc.2016.06.669 ◽

2016 ◽

Vol 25 ◽

pp. S285-S286

Author(s):

D. Zentner ◽

T. Thompson ◽

J. Taylor ◽

M. Bogwitz ◽

I. Macciocca ◽

...

Keyword(s):

Mutation Detection ◽

Gene Panel ◽

Panel Testing ◽

Gene Testing ◽

Gene Panel Testing

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Tu1673 – Single-Gene Vs. Multi-Gene Panel Testing in Management of Hereditary Gastrointestinal Cancer Syndromes

Gastroenterology ◽

10.1016/s0016-5085(19)39677-5 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-1086

Author(s):

Louise Wang ◽

John T. Nathanson ◽

Jessica Long ◽

Jessica Ebrahimzadeh ◽

Shria Kumar ◽

...

Keyword(s):

Gastrointestinal Cancer ◽

Single Gene ◽

Gene Panel ◽

Panel Testing ◽

Gene Panel Testing ◽

Cancer Syndromes

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Extended gene panel testing in lobular breast cancer

Familial Cancer ◽

10.1007/s10689-021-00241-5 ◽

2021 ◽

Author(s):

Elke M. van Veen ◽

D. Gareth Evans ◽

Elaine F. Harkness ◽

Helen J. Byers ◽

Jamie M. Ellingford ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Detection Rate ◽

Gene Panel ◽

Lobular Breast Cancer ◽

Germline Variants ◽

Panel Testing ◽

Pathogenic Variants ◽

Gene Panel Testing ◽

Increased Risk

AbstractPurpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.

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Clinical utility of a sponsored, no-cost skeletal dysplasia gene panel testing program: Results from 850 tests

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2020.12.238 ◽

2021 ◽

Vol 132 (2) ◽

pp. S98

Author(s):

Guillermo Seratti ◽

Vikram Pansare ◽

Tiffany Yar Pang ◽

Emanuela Izzo ◽

William Mackenzie ◽

...

Keyword(s):

Skeletal Dysplasia ◽

Clinical Utility ◽

Gene Panel ◽

Testing Program ◽

Panel Testing ◽

Gene Panel Testing

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Clinical utility of a sponsored, no-cost skeletal dysplasia gene panel testing program: results from 850 tests

Molecular Genetics and Metabolism ◽

10.1016/s1096-7192(21)00398-x ◽

2021 ◽

Vol 132 ◽

pp. S201

Author(s):

Guillermo Seratti ◽

Tiffany Pang ◽

Vikram Pansare ◽

Emanuela Izzo ◽

William Mackenzie ◽

...

Keyword(s):

Skeletal Dysplasia ◽

Clinical Utility ◽

Gene Panel ◽

Testing Program ◽

Panel Testing ◽

Gene Panel Testing

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Clinical implementation of gene panel testing for lysosomal storage diseases

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.527 ◽

2018 ◽

Vol 7 (2) ◽

Cited By ~ 2

Author(s):

Alexander Gheldof ◽

Sara Seneca ◽

Katrien Stouffs ◽

Willy Lissens ◽

Anna Jansen ◽

...

Keyword(s):

Lysosomal Storage Diseases ◽

Gene Panel ◽

Lysosomal Storage ◽

Clinical Implementation ◽

Storage Diseases ◽

Panel Testing ◽

Gene Panel Testing

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MS3-1 IMPLEMENTATION OF GENE PANEL TESTING USING NEXT-GENERATION SEQUENCING

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.011 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii3-ii3

Author(s):

Kazuko Sakai

Keyword(s):

Cancer Treatment ◽

Gene Mutation ◽

Diagnostic Testing ◽

Gene Panel ◽

Panel Testing ◽

Formalin Fixed Paraffin ◽

Gene Panel Testing ◽

Companion Diagnostic ◽

Formalin Fixed Paraffin Embedded ◽

Formalin Fixed

Abstract The advance of next-generation sequencers (NGS) has dramatically improved the performance of genomic analysis of clinical samples in cancer precision medicine. The practical use of gene panel testing for clinical applications has begun in Japan. At present, “OncomineTM Dx Target Test” is listed as a companion diagnostic system using NGS, and “FoundationOne CDx Cancer Genomic Profile” and “OncoGuide™ NCC Oncopanel System” are listed as gene panel testing under insurance coverage. Formalin-fixed paraffin-embedded specimen have been routinely used for molecular diagnosis testing, therefore quality control such as formalin fixation time and tumor contents is important to ensure validity of diagnostic results. In this presentation, the issue to obtain evaluable results of gene panel testing using formalin-fixed paraffin-embedded specimen will be discussed. Due to evolution of detection technologies, we can detect gene mutation with high sensitivity. Detection of gene mutation in circulating tumor DNA is feasible approach for diagnostic testing in cancer treatment. Liquid biopsy has been approved as a companion diagnostic testing to detect EGFR mutations in NSCLC. Examples of the clinical utility of plasma testing in cancer treatment will be presented.

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