MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors

Abstract Background MET amplification plays an important role in the development of non-small-cell lung cancer (NSCLC) either de novo or in resistance to epidermal growth factor receptor tyrosine–kinase inhibitor (EGFR-TKI) settings. Fluorescence in situ hybridization (FISH) is the standard method f...

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Autores principales:	Lun-Xi Peng, Guang-Ling Jie, An-Na Li, Si-Yang Liu, Hao Sun, Mei-Mei Zheng, Jia-Ying Zhou, Jia-Tao Zhang, Xu-Chao Zhang, Qing Zhou, Wen-Zhao Zhong, Jin-Ji Yang, Hai-Yan Tu, Jian Su, Hong-Hong Yan, Yi-Long Wu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	FISH-NGS MET amplification Predictive factors Survival benefits Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0d5dd8cd28a149f79236e148c0afbabe
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spelling	oai:doaj.org-article:0d5dd8cd28a149f79236e148c0afbabe2021-11-14T12:11:39ZMET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors10.1186/s40164-021-00245-y2162-3619https://doaj.org/article/0d5dd8cd28a149f79236e148c0afbabe2021-11-01T00:00:00Zhttps://doi.org/10.1186/s40164-021-00245-yhttps://doaj.org/toc/2162-3619Abstract Background MET amplification plays an important role in the development of non-small-cell lung cancer (NSCLC) either de novo or in resistance to epidermal growth factor receptor tyrosine–kinase inhibitor (EGFR-TKI) settings. Fluorescence in situ hybridization (FISH) is the standard method for MET amplification. With more and more discoveries of oncogenic driver genes, next-generation sequencing (NGS) plays a significant role in precision oncology. Meanwhile, the role of NGS in MET amplification remains uncertain. Methods Forty patients diagnosed with advanced NSCLC were included. FISH and NGS were conducted prior to MET inhibitors treatment. MET amplification by FISH was defined as a MET/CEP7 ratio of > 2.0 and/or copy number (CN) > 5. MET amplification by NGS was defined as gene copy number (GCN) ≥ 5. Results The concordance rate among FISH and NGS was 62.5% (25/40). MET amplification identified by FISH showed the optimal predictive value. The partial response (PR) rate was 68.0% (17/25 with MET amplification) vs. 6.7% (1/15 without MET amplification); the median progression-free survival (PFS) was 5.4 months versus 1.0 months (P < 0.001). MET amplification identified by NGS failed to distinguish significant clinical outcomes. The PR rate was 60.0% (6/10, with MET GCN ≥ 5) vs. 40.0% (12/30, with MET GCN < 5); the median PFS was 4.8 months vs. 2.2 months (P = 0.357). The PR rate was 68.8% (11/16) and the median PFS was 4.8 months in patients with focal amplification by NGS. Conclusions MET amplification identified by FISH remains the optimal biomarker to identify suitable candidates for MET-TKI therapy. In comparison, amplification identified by NGS seems not as robust to be effective predictive biomarker. Further exploration is needed regarding the focal amplification by NGS in predicting the efficacy.Lun-Xi PengGuang-Ling JieAn-Na LiSi-Yang LiuHao SunMei-Mei ZhengJia-Ying ZhouJia-Tao ZhangXu-Chao ZhangQing ZhouWen-Zhao ZhongJin-Ji YangHai-Yan TuJian SuHong-Hong YanYi-Long WuBMCarticleFISH-NGSMET amplificationPredictive factorsSurvival benefitsDiseases of the blood and blood-forming organsRC633-647.5Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENExperimental Hematology & Oncology, Vol 10, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FISH-NGS MET amplification Predictive factors Survival benefits Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	FISH-NGS MET amplification Predictive factors Survival benefits Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lun-Xi Peng Guang-Ling Jie An-Na Li Si-Yang Liu Hao Sun Mei-Mei Zheng Jia-Ying Zhou Jia-Tao Zhang Xu-Chao Zhang Qing Zhou Wen-Zhao Zhong Jin-Ji Yang Hai-Yan Tu Jian Su Hong-Hong Yan Yi-Long Wu MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors
description	Abstract Background MET amplification plays an important role in the development of non-small-cell lung cancer (NSCLC) either de novo or in resistance to epidermal growth factor receptor tyrosine–kinase inhibitor (EGFR-TKI) settings. Fluorescence in situ hybridization (FISH) is the standard method for MET amplification. With more and more discoveries of oncogenic driver genes, next-generation sequencing (NGS) plays a significant role in precision oncology. Meanwhile, the role of NGS in MET amplification remains uncertain. Methods Forty patients diagnosed with advanced NSCLC were included. FISH and NGS were conducted prior to MET inhibitors treatment. MET amplification by FISH was defined as a MET/CEP7 ratio of > 2.0 and/or copy number (CN) > 5. MET amplification by NGS was defined as gene copy number (GCN) ≥ 5. Results The concordance rate among FISH and NGS was 62.5% (25/40). MET amplification identified by FISH showed the optimal predictive value. The partial response (PR) rate was 68.0% (17/25 with MET amplification) vs. 6.7% (1/15 without MET amplification); the median progression-free survival (PFS) was 5.4 months versus 1.0 months (P < 0.001). MET amplification identified by NGS failed to distinguish significant clinical outcomes. The PR rate was 60.0% (6/10, with MET GCN ≥ 5) vs. 40.0% (12/30, with MET GCN < 5); the median PFS was 4.8 months vs. 2.2 months (P = 0.357). The PR rate was 68.8% (11/16) and the median PFS was 4.8 months in patients with focal amplification by NGS. Conclusions MET amplification identified by FISH remains the optimal biomarker to identify suitable candidates for MET-TKI therapy. In comparison, amplification identified by NGS seems not as robust to be effective predictive biomarker. Further exploration is needed regarding the focal amplification by NGS in predicting the efficacy.
format	article
author	Lun-Xi Peng Guang-Ling Jie An-Na Li Si-Yang Liu Hao Sun Mei-Mei Zheng Jia-Ying Zhou Jia-Tao Zhang Xu-Chao Zhang Qing Zhou Wen-Zhao Zhong Jin-Ji Yang Hai-Yan Tu Jian Su Hong-Hong Yan Yi-Long Wu
author_facet	Lun-Xi Peng Guang-Ling Jie An-Na Li Si-Yang Liu Hao Sun Mei-Mei Zheng Jia-Ying Zhou Jia-Tao Zhang Xu-Chao Zhang Qing Zhou Wen-Zhao Zhong Jin-Ji Yang Hai-Yan Tu Jian Su Hong-Hong Yan Yi-Long Wu
author_sort	Lun-Xi Peng
title	MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors
title_short	MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors
title_full	MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors
title_fullStr	MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors
title_full_unstemmed	MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors
title_sort	met amplification identified by next-generation sequencing and its clinical relevance for met inhibitors
publisher	BMC
publishDate	2021
url	https://doaj.org/article/0d5dd8cd28a149f79236e148c0afbabe
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MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors

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