ArticleTranslational lung cancer research2020
Tumor mutation burden derived from small next generation sequencing targeted gene panel as an initial screening method.
Article in Translational lung cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed.
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- Alterations in genomic features and the tumour immune microenvironment predict immunotherapy outcomes in advanced biliary tract cancer patients.British journal of cancer · 2025Article
- Mutation-guided chemotherapy-free strategy in first-line immunotherapy for low PD-L1-expressing non-squamous NSCLC.Journal for immunotherapy of cancer · 2024Article
- Systematic comparison of variant calling pipelines of target genome sequencing cross multiple next-generation sequencers.Frontiers in genetics · 2023Article
- Comprehensive clinical assays for molecular diagnostics of gliomas: the current state and future prospects.Frontiers in molecular biosciences · 2023Review
- Clinicopathological molecular characterizations of sinonasal NUT carcinoma: a report of two cases and a literature review.Frontiers in oncology · 2023Article
- The combination of gene hyperamplification and PD-L1 expression as a biomarker for the clinical benefit of tislelizumab in gastric/gastroesophageal junction adenocarcinoma.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples.Molecular diagnosis & therapy · 2022Article
- Liquid Biopsy Biomarkers for Immunotherapy in Non-Small Cell Lung Carcinoma: Lessons Learned and the Road Ahead.Journal of personalized medicine · 2021Review
- Deep Learning of Histopathological Features for the Prediction of Tumour Molecular Genetics.Diagnostics (Basel, Switzerland) · 2021Review
- Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer.Frontiers in oncology · 2020Article
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7 authors.
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Abstract
backgroundWith the increasing use of immune checkpoint inhibitors, tumor mutation burden (TMB) assessment is now routinely included in reports generated from targeted sequencing with large gene panels; however, not all patients require comprehensive profiling with large panels. Our study aims to explore the feasibility of using a small 56-gene panel as a screening method for TMB prediction.
methodsTMB from 406 non-small cell lung cancer (NSCLC) patients was estimated using a large 520-gene panel simulated with the prospective TMB status for the small panel. This information was then used to determine the optimal cut-off. An independent cohort of 30 NSCLC patients was sequenced with both panels to confirm the cut-off value.
resultsBy comparing sensitivity, specificity, and positive predictive value (PPV), the cut-off was set up as 10 mutations/megabase, yielding 81.4% specificity, 83.6% sensitivity, and 62.4% PPV. Further validation with an independent cohort sequenced with both panels using the same cut-off achieved 95.7% sensitivity, 71.4% specificity and 91.7% PPV. The decreasing trend of sensitivity with the increasing trend of both specificity and PPV with a concomitant increase in the cut-off for the small panel suggests that TMB is overestimated but highly unlikely to yield false-positive results. Hence, patients with low TMB (<10) can be reliably stratified from patients with high TMB (≥10).
conclusionsThe small panel, more cost-effective, can be used as a screening method to screen for patients with low TMB, while patients with TMB ≥10 are recommended for further validation with a larger panel.
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