scholarly journals Next-Generation Sequencing in Clinical Practice: Is It a Cost-Saving Alternative to a Single-Gene Testing Approach?

2021 ◽  
Author(s):  
Giancarlo Pruneri ◽  
Filippo De Braud ◽  
Anna Sapino ◽  
Massimo Aglietta ◽  
Andrea Vecchione ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Cost Saving ◽  
Single Gene ◽  
Next Generation ◽  
Gene Testing ◽  
Testing Approach ◽  
Generation Sequencing

Analysis of a large cohort of non-small cell lung cancers submitted for somatic variant analysis demonstrates that targeted next-generation sequencing is fit for purpose as a molecular diagnostic assay in routine practice

2018 ◽  
Vol 71 (11) ◽  
pp. 1001-1006 ◽  
Author(s):  
David Allan Moore ◽  
Kevin Balbi ◽  
Alexander Ingham ◽  
Hendrik-Tobias Arkenau ◽  
Philip Bennett
Keyword(s):  
Next Generation Sequencing ◽  
Single Gene ◽  
Small Cell ◽  
Molecular Diagnostic ◽  
Next Generation ◽  
Small Cell Lung ◽  
Targeted Next Generation Sequencing ◽  
Gene Testing ◽  
The Impact ◽  
Generation Sequencing

AimsTargeted next-generation sequencing (tNGS) is increasingly being adopted as an alternative to single gene testing in some centres. Our aim was to assess the overall fitness and utility of tNGS as a routine clinical test in non-small cell lung cancer (NSCLC).MethodsAll NSCLC cases submitted to a single laboratory for tNGS analysis over a 3-year period were included. Rejection/failure rates and turnaround times were calculated. For reportable cases, data relating to observed genetic changes likely to be driving tumour growth and/or contributing to therapeutic resistance were extracted. The impact of varied referral site practices (tissue processing and sample format submitted) on analytical outcomes was also considered.ResultsA total of 2796 cases were submitted, of which 217 (7.8%) were rejected and 131 (5.1%) failed. The median turnaround time was seven working days. Of 2448 reported cases, KRAS, EGFR or other recognised driver mutations were observed in 35%, 17% and 5.4%, respectively. Of the remaining cases, 3.5% demonstrated significant incidental evidence of gene amplification. In 15% of EGFR-driven cases, evidence of an EGFR tyrosine kinase inhibitor resistance mechanism was observed. Potential concerns around the provision of slides or precut ‘rolls’ only (cf, formalin fixed paraffin embedded (FFPE) tissue blocks) as standard practice by certain referral sites were identified.ConclusionsA tNGS panel approach is practically achievable, with acceptable success rates and turnaround times, in the context of a routine clinical service. Furthermore, it provides additional clinically and analytically relevant information, which is not available from single gene testing alone.

Next generation sequencing for detection of EGFR alterations in NSCLC: is more better?

2020 ◽  
pp. jclinpath-2020-207212
Author(s):  
Ullas Batra ◽  
Shrinidhi Nathany ◽  
Mansi Sharma ◽  
Parveen Jain ◽  
Anurag Mehta
Keyword(s):  
Next Generation Sequencing ◽  
Kinase Inhibitor ◽  
Single Gene ◽  
Next Generation ◽  
Cell Lung Carcinoma ◽  
Molecular Features ◽  
Gene Testing ◽  
Clinical Records ◽  
Egfr Mutated ◽  
Generation Sequencing

AimsThe emergence of sophisticated next generation sequencing (NGS) based technologies in routine molecular diagnostics has paved the way for robust and accurate detection of variants which may otherwise be missed on single gene testing. This study aims at highlighting the same premise in EGFR mutated non-small cell lung carcinoma (NSCLC).Methods1350 cases of NSCLC were screened, of which 490 EGFR mutated cases were taken. The clinical records and molecular features were evaluated retrospectively to determine those cases which were missed on single gene testing.ResultsAmong these 490 cases, there were 11 (2.2%) cases which tested negative on single gene testing using polymerase chain reaction (therascreen). These were then subjected to NGS based testing and were positive for 13 different EGFR mutations. Five out of the 11 cases received EGFR tyrosine kinase inhibitor (TKI) based on the NGS test outcome. Four cases with exon 20 insertion mutations were not offered TKI as these mutations are known to be intrinsically resistant to TKI therapy. The five patients who have been treated with TKI have shown fair response and have not progressed to date.ConclusionsWe demonstrated a potentially preferable way to profile treatment-naïve patients with NSCLC by NGS and from our early experience in EGFR mutant cases, the advantages of NGS over single gene testing is clearly evident.

scholarly journals Paroxysmal Movement Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Susan Harvey ◽  
Mary D. King ◽  
Kathleen M. Gorman
Keyword(s):  
Next Generation Sequencing ◽  
Movement Disorders ◽  
Clinical Phenotype ◽  
Single Gene ◽  
Copy Number Variant ◽  
Genomic Research ◽  
Next Generation ◽  
Causative Gene ◽  
Gene Testing ◽  
Generation Sequencing

Paroxysmal movement disorders (PxMDs) are a clinical and genetically heterogeneous group of movement disorders characterized by episodic involuntary movements (dystonia, dyskinesia, chorea and/or ataxia). Historically, PxMDs were classified clinically (triggers and characteristics of the movements) and this directed single-gene testing. With the advent of next-generation sequencing (NGS), how we classify and investigate PxMDs has been transformed. Next-generation sequencing has enabled new gene discovery (RHOBTB2, TBC1D24), expansion of phenotypes in known PxMDs genes and a better understanding of disease mechanisms. However, PxMDs exhibit phenotypic pleiotropy and genetic heterogeneity, making it challenging to predict genotype based on the clinical phenotype. For example, paroxysmal kinesigenic dyskinesia is most commonly associated with variants in PRRT2 but also variants identified in PNKD, SCN8A, and SCL2A1. There are no radiological or biochemical biomarkers to differentiate genetic causes. Even with NGS, diagnosis rates are variable, ranging from 11 to 51% depending on the cohort studied and technology employed. Thus, a large proportion of patients remain undiagnosed compared to other neurological disorders such as epilepsy, highlighting the need for further genomic research in PxMDs. Whole-genome sequencing, deep-sequencing, copy number variant analysis, detection of deep-intronic variants, mosaicism and repeat expansions, will improve diagnostic rates. Identifying the underlying genetic cause has a significant impact on patient care, modification of treatment, long-term prognostication and genetic counseling. This paper provides an update on the genetics of PxMDs, description of PxMDs classified according to causative gene rather than clinical phenotype, highlighting key clinical features and providing an algorithm for genetic testing of PxMDs.

scholarly journals Building a Robust Tumor Profiling Program: Synergy between Next-Generation Sequencing and Targeted Single-Gene Testing

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0152851 ◽  
Author(s):  
Matthew C. Hiemenz ◽  
Stephan Kadauke ◽  
David B. Lieberman ◽  
David B. Roth ◽  
Jianhua Zhao ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Single Gene ◽  
Next Generation ◽  
Gene Testing ◽  
Generation Sequencing ◽  
Tumor Profiling

scholarly journals Feasibility of next‐generation sequencing test for patients with advanced NSCLC in clinical practice

2020 ◽  
Author(s):  
Ryo Ariyasu ◽  
Ken Uchibori ◽  
Hironori Ninomiya ◽  
Shinsuke Ogusu ◽  
Ryosuke Tsugitomi ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Advanced Nsclc ◽  
Next Generation ◽  
Generation Sequencing

The novel approach to distinguish primary multiple lung adenocarcinomas from intrapulmonary metastases by next generation sequencing in Chinese patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20506-e20506
Author(s):  
Lin Li ◽  
Naiquan Mao ◽  
Yingcheng Lyu ◽  
Huayue Lin ◽  
Kefeng Wang ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Chinese Patients ◽  
Comparative Genomic ◽  
Genomic Profiling ◽  
Next Generation ◽  
Architectural Patterns ◽  
Chinese Cohort ◽  
Lung Adenocarcinomas ◽  
Generation Sequencing

e20506 Background: Differentiation of multiple primary lung cancer (MPLC) from intrapulmonary metastasis (IPM) is critical to determine clinical stage. Although clinicopathological features could provide certain evidences, it’s still challenging to identify the tumor malignancy accurately. In General, standard histopathologic approach is adequate in most cases, but has notable limitations in the recognition of IPMs. Herein, we propose an integrated molecular algorithm to facilitate MPLCs and IPMs diagnosis in the clinical practice. Methods: 40 Chinese patients with lung adenocarcinomas were enrolled in the study, 84 tumor samples were collected for next-generation sequencing. Somatic alterations with variant allele fraction (VAF) ≥1% were taken into account for molecular algorithm. A genomic database of 2,471 Chinese lung adenocarcinomas (LUAD) was used to calculate odds of coincidental occurrence, prevalence of individual mutation prevalence. Tumor relatedness diagnosed by histopathologic assessment was contrasted with comparative genomic profiling by subsequent NGS. Moreover, the performance of molecular algorithm prediction was evaluated as well. Results: Firstly, we compared the performance of comprehensive next-generation sequencing (NGS) with standard histopathologic approaches for distinguishing NSCLC subtypes in clinical practice. The genomic profiling was described as following: EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P<0.05). Further analysis showed that TP53 alterations occurred less frequently in MPLCs compared to large Chinese cohort (22.9% vs 51.0%, P<0.05). TP53 alterations occurred less frequently in MPLCs compared to large Chinese cohort (P<0.05). The classifications based on the three different methodologies mentioned above were compared. Molecular algorithm prediction was concordant with NGS in 21 cases (52.5%), particularly in the prediction of MPLC. Retrospective review highlighted several histologic challenges, including morphologic progression in some IPMs. For the five undetermined cases, two showed differences in architectural patterns, and remained cases have nodules presented as adenocarcinoma in situ, or minimally invasive adenocarcinoma. Of 28 MPLC cases defined by NGS, 25 cases had unique somatic mutations per pair Based on calculation from the prevalence of EGFR L858R mutation (27%) in large Chinese cohort, the odds of coincidental occurrence of the mutation in two unrelated tumors was 7.3%. Taking together, EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P<0.05). Molecular algorithm prediction was concordant with NGS in 21 cases (52.5%). Conclusions: Our results support broad panel NGS to assist differential diagnosis to assist approach in clinical practice. It is necessary to conduct large clinical study to establish comprehensive algorithm models to assist diagnosis and predict clinical outcome.

scholarly journals Integrating a Next Generation Sequencing Panel into Clinical Practice in Ovarian Cancer

2019 ◽  
Vol 60 (10) ◽  
pp. 914 ◽  
Author(s):  
Yong Jae Lee ◽  
Dachan Kim ◽  
Hyun-Soo Kim ◽  
Kiyong Na ◽  
Jung-Yun Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Generation Sequencing
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