Feasibility of Low-Throughput Next Generation Sequencing for Germline DNA Screening

Sapari, Nur Sabrina; Elahi, Eiram; Wu, Mengchu; Loh, Marie; Ng, Hong Kiat; Han, Xiao; Yap, Hui Ling; Klemm, T; Pang, Brendan; Benoukraf, Touati; Teo, Yik Ying; Iacopetta, Barry; Lee, Soo‐Chin; Soong, Richie

doi:10.1373/clinchem.2014.227728

Cited by 6 publications

(3 citation statements)

References 39 publications

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“…High performance standards are essential in the clinical diagnostic setting122125262728. The critical difference between panel sequencing and WES is coverage.…”

Section: Discussionmentioning

confidence: 99%

Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

Feliubadaló

Tonda

Gausachs

et al. 2017

Sci Rep

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Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set). TruSight Cancer (94 genes) and a custom panel (122 genes) were assessed alongside exome sequencing. Eighty-three genes were targeted by the two panels and exome sequencing. More than 99% of bases had a read depth of over 30x in the panels, whereas exome sequencing covered 94%. Variant calling with standard settings identified the 10 mutations in the control set, with the exception of MSH6 c.255dupC using TruSight Cancer. In the discovery set, 240 unique non-silent coding and canonic splice-site variants were identified in the panel genes, 7 of them putatively pathogenic (in ATM, BARD1, CHEK2, ERCC3, FANCL, FANCM, MSH2). The three approaches identified a similar number of variants in the shared genes. Exomes were more expensive than panels but provided additional data. In terms of cost and depth, panels are a suitable option for genetic diagnostics, although exomes also identify variants in non-targeted genes.

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“…High performance standards are essential in the clinical diagnostic setting122125262728. The critical difference between panel sequencing and WES is coverage.…”

Section: Discussionmentioning

confidence: 99%

Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

Feliubadaló

Tonda

Gausachs

et al. 2017

Sci Rep

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“…This greatly necessitates the need for counseling before and after testing by genetic counselors and knowledgeable clinicians. As illustrated in the feasibility study by Sapari et al, 41 developing a robust analysis pipeline and clinically valid databases are essential in the interpretation of these NGS results. In their study, they performed NGS for germline DNA LS testing by using a low-throughput assay, the TruSight Cancer Panel (Illumina Q8 , San Diego, CA) on the MiSeq System (Illumina).…”

Section: Ngs As a Diagnostic Tool In Lsmentioning

confidence: 99%

Targeted Next-Generation Sequencing for Hereditary Cancer Syndromes

Tafe

2015

The Journal of Molecular Diagnostics

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Lynch syndrome is a hereditary cancer syndrome that results from germline mutations in one of the DNA mismatch repair genes, leading to an increased lifetime risk of cancer. Colorectal cancer is most commonly identified with Lynch syndrome; however, women with Lynch syndrome have an increased risk of developing endometrial cancer (up to 60%), which is the sentinel diagnosis in approximately one-half of the cases. Current screening algorithms are developed on family history and laboratory-based tests, including immunohistochemistry for mismatch repair proteins and microsatellite instability testing. Next-generation sequencing assays are rapidly being incorporated into clinical laboratory practices and have diagnostic applications for hereditary cancer syndromes. Important challenges of next-generation sequencing include interpreting incidental and uncertain findings, counseling before and after testing, and informed consent of patients. Here, with the use of Lynch syndrome in endometrial cancer as a model, some of the applications and intricacies of next-generation sequencing testing for hereditary cancer syndromes are reviewed.

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“…Genetic testing using the next-generation sequencing (NGS) analysis is becoming increasingly recommended for cancer diagnosis and treatment decision-making (1,2). Traditionally, the NGS technique was applied to tumor tissues to examine gene alterations related to specific cancers (3,4).…”

Section: Introductionmentioning

confidence: 99%

Genomic alteration profiles of lung cancer and their relationship to clinical features and prognosis value using individualized genetic testing

Zhang¹,

Wang²,

Ma³

et al. 2021

J Thorac Dis

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This study aimed to use a panel targeting 197 genes and 38 fusions to observe the features of gene variations in lung cancer patients, as well as their prognostic values. Methods:Patients admitted to our hospital between 2016 and 2017 were enrolled. All patients received OseqTM-Drug genetic testing using peripheral venous blood, followed by 1-2 years of observation. Results:For all included patients, 32 genes were observed with mutations. EGFR exhibited the highest mutation rate (46.5%), followed by TP53. The majority of patients carried only one mutant gene. Interestingly, 18 (41.8%) patients showed no mutations, and some cases carried mutations in six genes simultaneously. There was no statistical relationship between mutations and demographic influence.Pathological subtypes were associated with mutations including FLI1, IGF1R, and NOTCH1. A significant correlation was observed between mutant genes and stage at diagnosis, however this requires further confirmation as there was only one case in these mutations: AKT2, AR, STK11, VEGFA, HDAC6, and ASPSCR. For the 33 patients with lymph node metastases at the time of diagnosis, no correlation with any gene mutant was found. Finally, no associations between the survival or prognosis indices (1-year survival, 1-year progression, progression free survival (PFS), and overall survival (OS)) were observed with gene mutations. Conclusions:Together, individualized genetic testing is a feasible and minimally invasive approach in cancer genetic analysis. However, gene mutation detection has a limited efficacy in the prediction of prognosis.

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Feasibility of Low-Throughput Next Generation Sequencing for Germline DNA Screening

Cited by 6 publications

References 39 publications

Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

Targeted Next-Generation Sequencing for Hereditary Cancer Syndromes

Genomic alteration profiles of lung cancer and their relationship to clinical features and prognosis value using individualized genetic testing

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