scholarly journals Tumour mutational burden ring trial: Evaluation of targeted next-generation sequencing platforms for implementation in clinical practice

2019 ◽  
Vol 30 ◽  
pp. xi10
Author(s):  
S. Lambin ◽  
D. Lambrechts ◽  
C. De Rop ◽  
N. D'Haene ◽  
G. Froyen ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Mutational Burden ◽  
Ring Trial ◽  
Sequencing Platforms ◽  
Generation Sequencing

scholarly journals Targeted Next-Generation Sequencing of Cancer-Related Genes in a Norwegian Patient Cohort With Head and Neck Squamous Cell Carcinoma Reveals Novel Actionable Mutations and Correlations With Pathological Parameters

2021 ◽  
Vol 11 ◽  
Author(s):  
Harsh N. Dongre ◽  
Hilde Haave ◽  
Siren Fromreide ◽  
Fredrik A. Erland ◽  
Svein Erik Emblem Moe ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Head And Neck ◽  
Squamous Cell ◽  
Ffpe Tissue ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Mutational Burden ◽  
Custom Made ◽  
Targeted Ngs ◽  
Generation Sequencing

BackgroundTargeted next-generation sequencing (NGS) is increasingly applied in clinical oncology to advance personalized treatment. Despite success in many other tumour types, use of targeted NGS panels for assisting diagnosis and treatment of head and neck squamous cell carcinomas (HNSCC) is still limited.AimThe focus of this study was to establish a robust NGS panel targeting most frequent cancer mutations in long-term preserved formalin-fixed paraffin-embedded (FFPE) tissue samples of HNSCC from routine diagnostics.Materials and MethodsTumour DNA obtained from archival FFPE tissue blocks of HNSCC patients treated at Haukeland University Hospital between 2003-2016 (n=111) was subjected to mutational analysis using a custom made AmpliSeq Library PLUS panel targeting 31 genes (Illumina). Associations between mutational burden and clinical and pathological parameters were investigated. Mutation and corresponding clinicopathological data from HNSCC were extracted for selected genes from the Cancer Genome Atlas (TCGA) and used for Chi-square and Kaplan-Meier analysis.ResultsThe threshold for sufficient number of reads was attained in 104 (93.7%) cases. Although the specific number of PCR amplified reads detected decreased, the number of NGS-annotated mutations did not significantly change with increased tissue preservation time. In HPV-negative carcinomas, mutations were detected mainly in TP53 (73.3%), FAT1 (26.7%) and FLG (16.7%) whereas in HPV-positive, the common mutations were in FLG (24.3%) FAT1 (17%) and FGFR3 (14.6%) genes. Other less common pathogenic mutations, including well reported SNPs were reproducibly identified. Presence of at least one cancer-specific mutations was found to be positively associated with an extensive desmoplastic stroma (p=0.019), and an aggressive type of invasive front (p=0.035), and negatively associated with the degree of differentiation (p=0.041). Analysis of TCGA data corroborated the association between cancer-specific mutations and tumour differentiation and survival analysis showed that tumours with at least one mutation had shorter disease-free and overall survival (p=0.005).ConclusionsA custom made targeted NGS panel could reliably detect several specific mutations in archival samples of HNSCCs preserved up to 17 years. Using this method novel associations between mutational burden and clinical and pathological parameters were detected and actionable mutations in HPV-positive HNSCC were discovered.

scholarly journals The Genetic Germline Background of Single and Multiple Primary Melanomas

2021 ◽  
Vol 7 ◽  
Author(s):  
Simona De Summa ◽  
Antonia Lasorella ◽  
Sabino Strippoli ◽  
Giuseppe Giudice ◽  
Gabriella Guida ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Cell Cycle Control ◽  
Germline Mutations ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Multiple Genes ◽  
Multiple Primary ◽  
Small Cohort ◽  
Sequencing Platforms ◽  
Generation Sequencing

Background:Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel.Materials and Methods:A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence.Results:We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs,p= 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p= 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development.Conclusions:In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM.

scholarly journals Qualification of tumour mutational burden by targeted next‐generation sequencing as a biomarker in hepatocellular carcinoma

2020 ◽  
Vol 41 (1) ◽  
pp. 192-203 ◽  
Author(s):  
Ching Ngar Wong ◽  
Petros Fessas ◽  
Kathy Dominy ◽  
Francesco A. Mauri ◽  
Takahiro Kaneko ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Mutational Burden ◽  
Generation Sequencing

scholarly journals Applying Next-Generation Sequencing Platforms for Pharmacogenomic Testing in Clinical Practice

2021 ◽  
Vol 12 ◽  
Author(s):  
Alireza Tafazoli ◽  
Henk-Jan Guchelaar ◽  
Wojciech Miltyk ◽  
Adam J. Kretowski ◽  
Jesse J. Swen
Keyword(s):  
Clinical Practice ◽  
Drug Therapy ◽  
Next Generation Sequencing ◽  
Cost Effective ◽  
Genetic Data ◽  
Next Generation ◽  
Cost Effective Approach ◽  
Sequencing Platforms ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Pharmacogenomics (PGx) studies the use of genetic data to optimize drug therapy. Numerous clinical centers have commenced implementing pharmacogenetic tests in clinical routines. Next-generation sequencing (NGS) technologies are emerging as a more comprehensive and time- and cost-effective approach in PGx. This review presents the main considerations for applying NGS in guiding drug treatment in clinical practice. It discusses both the advantages and the challenges of implementing NGS-based tests in PGx. Moreover, the limitations of each NGS platform are revealed, and the solutions for setting up and management of these technologies in clinical practice are addressed.

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