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Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics

The recent increase in the number of molecular targeted agents for lung cancer has led to the demand for the simultaneous testing of multiple genes. Although gene panels using next-generation sequencing (NGS) are ideal, conventional panels require a high tumor content, and biopsy samples often do no...

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Autores principales: Kato, Kikuya, Okami, Jiro, Nakamura, Harumi, Honma, Keiichiro, Sato, Yoshiharu, Nakamura, Seiji, Kukita, Yoji, Nakatsuka, Shin-ichi, Higashiyama, Masahiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137435/
https://www.ncbi.nlm.nih.gov/pubmed/37189577
http://dx.doi.org/10.3390/diagnostics13081476
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author Kato, Kikuya
Okami, Jiro
Nakamura, Harumi
Honma, Keiichiro
Sato, Yoshiharu
Nakamura, Seiji
Kukita, Yoji
Nakatsuka, Shin-ichi
Higashiyama, Masahiko
author_facet Kato, Kikuya
Okami, Jiro
Nakamura, Harumi
Honma, Keiichiro
Sato, Yoshiharu
Nakamura, Seiji
Kukita, Yoji
Nakatsuka, Shin-ichi
Higashiyama, Masahiko
author_sort Kato, Kikuya
collection PubMed
description The recent increase in the number of molecular targeted agents for lung cancer has led to the demand for the simultaneous testing of multiple genes. Although gene panels using next-generation sequencing (NGS) are ideal, conventional panels require a high tumor content, and biopsy samples often do not meet this requirement. We developed a new NGS panel, called compact panel, characterized by high sensitivity, with detection limits for mutations of 0.14%, 0.20%, 0.48%, 0.24%, and 0.20% for EGFR exon 19 deletion, L858R, T790M, BRAF V600E, and KRAS G12C, respectively. Mutation detection also had a high quantitative ability, with correlation coefficients ranging from 0.966 to 0.992. The threshold for fusion detection was 1%. The panel exhibited good concordance with the approved tests. The identity rates were as follows: EGFR positive, 100% (95% confidence interval, 95.5–100); EGFR negative, 90.9 (82.2–96.3); BRAF positive, 100 (59.0–100); BRAF negative, 100 (94.9–100); KRAS G12C positive, 100 (92.7–100); KRAS G12C negative, 100 (93.0–100); ALK positive, 96.7 (83.8–99.9); ALK negative, 98.4 (97.2–99.2); ROS1 positive, 100 (66.4–100); ROS1 negative, 99.0 (94.6–100); MET positive, 98.0 (89.0–99.9); MET negative 100 (92.8–100); RET positive, 93.8 (69.8–100); RET negative, 100 (94.9–100). The analytical performance showed that the panel could handle various types of biopsy samples obtained by routine clinical practice without requiring strict pathological monitoring, as in the case of conventional NGS panels.
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spelling pubmed-101374352023-04-28 Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics Kato, Kikuya Okami, Jiro Nakamura, Harumi Honma, Keiichiro Sato, Yoshiharu Nakamura, Seiji Kukita, Yoji Nakatsuka, Shin-ichi Higashiyama, Masahiko Diagnostics (Basel) Article The recent increase in the number of molecular targeted agents for lung cancer has led to the demand for the simultaneous testing of multiple genes. Although gene panels using next-generation sequencing (NGS) are ideal, conventional panels require a high tumor content, and biopsy samples often do not meet this requirement. We developed a new NGS panel, called compact panel, characterized by high sensitivity, with detection limits for mutations of 0.14%, 0.20%, 0.48%, 0.24%, and 0.20% for EGFR exon 19 deletion, L858R, T790M, BRAF V600E, and KRAS G12C, respectively. Mutation detection also had a high quantitative ability, with correlation coefficients ranging from 0.966 to 0.992. The threshold for fusion detection was 1%. The panel exhibited good concordance with the approved tests. The identity rates were as follows: EGFR positive, 100% (95% confidence interval, 95.5–100); EGFR negative, 90.9 (82.2–96.3); BRAF positive, 100 (59.0–100); BRAF negative, 100 (94.9–100); KRAS G12C positive, 100 (92.7–100); KRAS G12C negative, 100 (93.0–100); ALK positive, 96.7 (83.8–99.9); ALK negative, 98.4 (97.2–99.2); ROS1 positive, 100 (66.4–100); ROS1 negative, 99.0 (94.6–100); MET positive, 98.0 (89.0–99.9); MET negative 100 (92.8–100); RET positive, 93.8 (69.8–100); RET negative, 100 (94.9–100). The analytical performance showed that the panel could handle various types of biopsy samples obtained by routine clinical practice without requiring strict pathological monitoring, as in the case of conventional NGS panels. MDPI 2023-04-19 /pmc/articles/PMC10137435/ /pubmed/37189577 http://dx.doi.org/10.3390/diagnostics13081476 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kato, Kikuya
Okami, Jiro
Nakamura, Harumi
Honma, Keiichiro
Sato, Yoshiharu
Nakamura, Seiji
Kukita, Yoji
Nakatsuka, Shin-ichi
Higashiyama, Masahiko
Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics
title Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics
title_full Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics
title_fullStr Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics
title_full_unstemmed Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics
title_short Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics
title_sort analytical performance of a highly sensitive system to detect gene variants using next-generation sequencing for lung cancer companion diagnostics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137435/
https://www.ncbi.nlm.nih.gov/pubmed/37189577
http://dx.doi.org/10.3390/diagnostics13081476
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